Judith Bovee's Publications List

Identification of a novel, recurrent HEY1-NCOA2 fusion in mesenchymal chondrosarcoma based on a genome-wide screen of exon-level expression data.

2012-03-06T21:29:47Z

Cancer gene fusions that encode a chimeric protein are often characterized by an intragenic discontinuity in the RNA\expression levels of the exons that are 5' or 3' to the fusion point in one or both of the fusion partners due to differences in the levels of activation of their respective promoters. Based on this, we developed an unbiased, genome-wide bioinformatic screen for gene fusions using A...

Lu Wang, Toru Motoi, Raya Khanin, Adam Olshen, Fredrik Mertens, Julia Bridge, Paola Dal Cin, Cristina R Antonescu, Samuel Singer, Meera Hameed, Judith V M G Bovee, Pancras C W Hogendoorn, Nicholas Socci, Marc Ladanyi (2012) Genes Chromosomes Cancer 51: 2 127-139

Peripheral chondrosarcoma progression is associated with increased type X collagen and vascularisation.

2012-07-31T14:05:33Z

Endochondral bone formation requires a cartilage template, known as the growth plate, and vascular invasion, bringing osteoblasts and osteoclasts. Endochondral chondrocytes undergo sequences of cell division, matrix secretion, cell hypertrophy, apoptosis, and matrix calcification/mineralisation. In this study, two critical steps of endochondral bone formation, the deposition of collagen X-rich mat...

Carlos E de Andrea, Malgorzata I Wiweger, Judith V M G Bovée, Salvatore Romeo, Pancras C W Hogendoorn (2012) Virchows Arch 460: 1 95-102

FUS rearrangements are rare in 'pure' sclerosing epithelioid fibrosarcoma.

2012-07-31T14:05:33Z

Several recent reports have described low-grade fibromyxoid sarcoma with sclerosing epithelioid fibrosarcoma-like areas. We evaluated cases of pure sclerosing epithelioid fibrosarcoma lacking areas of low-grade fibromyxoid sarcoma for FUS rearrangement to determine whether this entity could be related to low-grade fibromyxoid sarcoma. Available formalin-fixed paraffin-embedded tissue of 27 scleros...

Wei-Lien Wang, Harry L Evans, Jeanne M Meis, Bernadette Liegl-Atzwanger, Judith V M G Bovee, John R Goldblum, Steven D Billings, Brian P Rubin, Dolores López-Terrada, Alexander J Lazar (2012) Mod Pathol 25: 6 846-853

Increased type II deiodinase protein in OA-affected cartilage and allelic imbalance of OA risk polymorphism rs225014 at DIO2 in human OA joint tissues.

2012-07-31T14:05:33Z

Genetic variation at the type II deiodinase (D2) gene (DIO2) was previously identified as osteoarthritis (OA) risk factor. To investigate mechanisms possibly underlying this association, we assessed D2 protein in healthy and OA-affected cartilage and investigated allelic balance of the OA risk polymorphism rs225014 at DIO2 in human OA joints.

Steffan D Bos, Judith V M G Bovée, Bouke J Duijnisveld, Emma V A Raine, Wouter J van Dalen, Yolande F M Ramos, Ruud van der Breggen, Rob G H H Nelissen, P Eline Slagboom, John Loughlin, Ingrid Meulenbelt (2012) Ann Rheum Dis 71: 7 1254-1258

Involvement of the PI3K/Akt pathway in myxoid/round cell liposarcoma.

2012-03-06T21:29:47Z

The molecular determinants involved in the progression of myxoid liposarcoma to increased cellularity/round cell change are poorly understood. We studied the PI3K/Akt pathway in myxoid and round cell liposarcomas using a tissue microarray composed of 165 tumors from 111 patients, and mutational analysis of PIK3CA in 44 cases. Activating PIK3CA mutations were found in 6/44 cases, 14%; mutations wer...

Elizabeth G Demicco, Keila E Torres, Markus P Ghadimi, Chiara Colombo, Svetlana Bolshakov, Aviad Hoffman, Tingsheng Peng, Judith V M G Bovée, Wei-Lien Wang, Dina Lev, Alexander J Lazar (2012) Mod Pathol 25: 2 212-221

Digital fibromyxoma (superficial acral fibromyxoma): a detailed characterization of 124 cases.

2012-07-31T14:05:33Z

Digital fibromyxoma (first described by Fetsch and colleagues as superficial acral fibromyxoma) is a distinctive soft tissue tumor with a predilection for the subungual or periungual region of the hands and feet. This report details the histologic, immunophenotypic, and clinical findings in 124 cases of digital fibromyxoma. The study group included 70 male and 54 female patients (1.3:1, M:F), rang...

Travis J Hollmann, Judith V M G Bovée, Christopher D M Fletcher (2012) Am J Surg Pathol 36: 6 789-798

NR4A3 rearrangement reliably distinguishes between the clinicopathologically overlapping entities myoepithelial carcinoma of soft tissue and cellular extraskeletal myxoid chondrosarcoma.

2012-07-31T14:05:33Z

Myoepithelial carcinoma of soft tissue (MEC) and cellular extraskeletal myxoid chondrosarcoma (cEMC) share striking similarities. In this paper, we compare ten MECs with five cEMCs. MEC patients had an equal gender distribution. The age range was 15-76 years (mean, 42 years). Tumours were located on extremities, pelvic girdle, vulva and neck. Follow-up, available for nine patients, ranged from 4...

Uta Flucke, Bastiaan B J Tops, Marian A J Verdijk, Patricia J H van Cleef, Peter H van Zwam, Pieter J Slootweg, Judith V M G Bovée, Robert G Riedl, David H Creytens, Albert J H Suurmeijer, Thomas Mentzel (2012) Virchows Arch 460: 6 621-628

Genetic characterization of mesenchymal, clear cell, and dedifferentiated chondrosarcoma.

2012-07-31T14:05:33Z

Clear cell, mesenchymal, and dedifferentiated chondrosarcoma are rare, cartilaginous tumors with limited treatment options other than surgery. Conventional chondrosarcomas have been extensively studied at the genetic level, but for rare chondrosarcoma subtypes, this is merely restricted to case reports. Information on the genetics of rare chondrosarcomas may provide insight into the etiology of th...

Danielle Meijer, Danielle de Jong, Twinkal C Pansuriya, Brendy E van den Akker, Piero Picci, Karoly Szuhai, Judith V G M Bovée (2012) Genes Chromosomes Cancer :

Interobserver reliability in the histopathological diagnosis of cartilaginous tumors in patients with multiple osteochondromas.

2012-07-31T14:05:33Z

The distinction between benign and malignant cartilaginous tumors located peripherally in the bone may be a challenging task in surgical pathology. The aim of this study was to investigate interobserver reliability in histological diagnosis of cartilaginous tumors in the setting of multiple osteochondromas and to evaluate possible histological parameters that could differentiate among osteochondro...

Carlos E de Andrea, Herman M Kroon, Ron Wolterbeek, Salvatore Romeo, Andrew E Rosenberg, Barry R De Young, Bernadette Liegl, Carrie Y Inwards, Esther Hauben, Edward F McCarthy, Miguel Idoate, Nicholas A Athanasou, Kevin B Jones, Pancras Cw Hogendoorn, Judith V M G Bovée (2012) Mod Pathol :

Molecular pathology and its diagnostic use in bone tumors.

2012-07-31T14:05:33Z

Bone tumors are considered by most pathologists difficult to diagnose as they are rare, have overlapping morphology, need radiological correlation, and the usefulness of immunohistochemistry is limited, making conventional morphology the cornerstone of the diagnosis. Over the past decade, more and more has become known of the molecular background of bone tumors. Three groups of bone tumors are rec...

Karoly Szuhai, Anne-Marie Cleton-Jansen, Pancras C W Hogendoorn, Judith V M G Bovée (2012) Cancer Genet 205: 5 193-204

Tiling resolution array-CGH shows that somatic mosaic deletion of the EXT gene is causative in EXT gene mutation negative multiple osteochondromas patients.

2011-05-18T14:41:59Z

Multiple osteochondromas (MO) is a hereditary skeletal disorder characterized by the presence of cartilage capped bony outgrowths at bone surface. Causative mutations in EXT1 or EXT2 genes have been described in 85-90 % of MO cases. However, in about 10-15 % of the MO cases, genomic alterations can not be detected, implying the potential role of other alterations. We have designed a custom-made Ag...

Károly Szuhai, Ivy Jennes, Danielle de Jong, Judith V M G Bovée, Malgorzata Wiweger, Wim Wuyts, Pancras C W Hogendoorn (2011) Hum Mutat 32: 2 E2036-E2049

Vascular tumors of bone: imaging findings.

2011-05-18T14:41:59Z

To identify radiological features of malignant vascular tumors of bone, which can be used to avoid erroneously diagnosing metastases based on radiological multifocality, and histological epitheloid phenotype.

Marieke Vermaat, Daniel Vanel, Herman M Kroon, Sofie L J Verbeke, Marco Alberghini, Judith V M G Bovee, Johan L Bloem (2011) Eur J Radiol 77: 1 13-18

Distinct histological features characterize primary angiosarcoma of bone.

2012-03-06T21:29:00Z

To define the histological criteria of primary angiosarcoma of bone.

Sofie L J Verbeke, Franco Bertoni, Patrizia Bacchini, Raf Sciot, Christopher D M Fletcher, Herman M Kroon, Pancras C W Hogendoorn, Judith V M G Bovée (2011) Histopathology 58: 2 254-264

Loss-of-function mutations in PTPN11 cause metachondromatosis, but not Ollier disease or Maffucci syndrome.

2012-03-06T21:29:00Z

Metachondromatosis (MC) is a rare, autosomal dominant, incompletely penetrant combined exostosis and enchondromatosis tumor syndrome. MC is clinically distinct from other multiple exostosis or multiple enchondromatosis syndromes and is unlinked to EXT1 and EXT2, the genes responsible for autosomal dominant multiple osteochondromas (MO). To identify a gene for MC, we performed linkage analysis with...

Margot E Bowen, Eric D Boyden, Ingrid A Holm, Belinda Campos-Xavier, Luisa Bonafé, Andrea Superti-Furga, Shiro Ikegawa, Valerie Cormier-Daire, Judith V Bovée, Twinkal C Pansuriya, Sérgio B de Sousa, Ravi Savarirayan, Elena Andreucci, Miikka Vikkula, Livia Garavelli, Caroline Pottinger, Toshihiko Ogino, Akinori Sakai, Bianca M Regazzoni, Wim Wuyts, Luca Sangiorgi, Elena Pedrini, Mei Zhu, Harry P Kozakewich, James R Kasser, Jon G Seidman, Kyle C Kurek, Matthew L Warman (2011) PLoS Genet 7: 4

Clonal evolution through loss of chromosomes and subsequent polyploidization in chondrosarcoma.

2012-03-06T21:29:47Z

Near-haploid chromosome numbers have been found in less than 1% of cytogenetically reported tumors, but seem to be more common in certain neoplasms including the malignant cartilage-producing tumor chondrosarcoma. By a literature survey of published karyotypes from chondrosarcomas we could confirm that loss of chromosomes resulting in hyperhaploid-hypodiploid cells is common and that these cells m...

Linda Olsson, Kajsa Paulsson, Judith V M G Bovée, Karolin H Nord (2011) PLoS One 6: 9

Maffucci syndrome: a genome-wide analysis using high resolution single nucleotide polymorphism and expression arrays on four cases.

2012-03-06T21:29:00Z

Ollier disease and Maffucci syndrome are rare, nonhereditary skeletal disorders characterized by the presence of multiple enchondromas with (Maffucci) or without (Ollier) co-existing multiple hemangiomas of soft tissue. Enchondromas can progress toward central chondrosarcomas. PTH1R mutations are found in a small subset of Ollier patients. The genetic deficit in Maffucci syndrome is unknown. Here,...

Twinkal C Pansuriya, Jan Oosting, Suzan H M Verdegaal, Adrienne M Flanagan, Raf Sciot, Lars-Gunnar Kindblom, Pancras C W Hogendoorn, Karoly Szuhai, Judith V M G Bovée (2011) Genes Chromosomes Cancer 50: 9 673-679

Genome-wide analysis of Ollier disease: Is it all in the genes?

2011-05-18T14:41:59Z

Ollier disease is a rare, non-hereditary disorder which is characterized by the presence of multiple enchondromas (ECs), benign cartilaginous neoplasms arising within the medulla of the bone, with an asymmetric distribution. The risk of malignant transformation towards central chondrosarcoma (CS) is increased up to 35%. The aetiology of Ollier disease is unknown.

Twinkal C Pansuriya, Jan Oosting, Tibor Krenács, Antonie H M Taminiau, Suzan H M Verdegaal, Luca Sangiorgi, Raf Sciot, Pancras C W Hogendoorn, Karoly Szuhai, Judith V M G Bovée (2011) Orphanet J Rare Dis 6:

Opening the archives for state of the art tumour genetic research: sample processing for array-CGH using decalcified, formalin-fixed, paraffin-embedded tissue-derived DNA samples.

2012-03-06T21:29:00Z

Molecular genetic studies on rare tumour entities, such as bone tumours, often require the use of decalcified, formalin-fixed, paraffin-embedded tissue (dFFPE) samples. Regardless of which decalcification procedure is used, this introduces a vast breakdown of DNA that precludes the possibility of further molecular genetic testing. We set out to establish a robust protocol that would overcome these...

Danielle de Jong, Sofie Lj Verbeke, Danielle Meijer, Pancras Cw Hogendoorn, Judith Vmg Bovee, Károly Szuhai (2011) BMC Res Notes 4:

Multiple statistical analysis techniques corroborate intratumor heterogeneity in imaging mass spectrometry datasets of myxofibrosarcoma.

2012-03-06T21:29:47Z

MALDI mass spectrometry can generate profiles that contain hundreds of biomolecular ions directly from tissue. Spatially-correlated analysis, MALDI imaging MS, can simultaneously reveal how each of these biomolecular ions varies in clinical tissue samples. The use of statistical data analysis tools to identify regions containing correlated mass spectrometry profiles is referred to as imaging MS-ba...

Emrys A Jones, Alexandra van Remoortere, René J M van Zeijl, Pancras C W Hogendoorn, Judith V M G Bovée, André M Deelder, Liam A McDonnell (2011) PLoS One 6: 9

Restoration of chemosensitivity for doxorubicin and cisplatin in chondrosarcoma in vitro: BCL-2 family members cause chemoresistance.

2012-03-06T21:29:47Z

BACKGROUND: Chondrosarcomas are malignant cartilage-forming tumors notorious for their resistance to conventional chemo- and radiotherapy. Postulated explanations describe the inaccessibility due to abundant hyaline cartilaginous matrix, presence of multidrug resistance (MDR) pumps, and expression of anti-apoptotic BCL-2 family members.Materials and methods: We studied the sensitivity of chondrosa...

J G van Oosterwijk, B Herpers, D Meijer, I H Briaire-de Bruijn, A M Cleton-Jansen, H Gelderblom, B van de Water, J V M G Bovée (2011) Ann Oncol :

Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome.

2012-03-06T21:29:47Z

Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). We report somatic heterozygous mutations in IDH1 (c.394C>T encoding an R132C substitution and c.395G>A encoding an R132H substitution) or IDH2 (c.516G>C encoding R172S) in 87% of enchondromas (benign cartilage...

Twinkal C Pansuriya, Ronald van Eijk, Pio d'Adamo, Maayke A J H van Ruler, Marieke L Kuijjer, Jan Oosting, Anne-Marie Cleton-Jansen, Jolieke G van Oosterwijk, Sofie L J Verbeke, Daniëlle Meijer, Tom van Wezel, Karolin H Nord, Luca Sangiorgi, Berkin Toker, Bernadette Liegl-Atzwanger, Mikel San-Julian, Raf Sciot, Nisha Limaye, Lars-Gunnar Kindblom, Soeren Daugaard, Catherine Godfraind, Laurence M Boon, Miikka Vikkula, Kyle C Kurek, Karoly Szuhai, Pim J French, Judith V M G Bovée (2011) Nat Genet 43: 12 1256-1261

Expression of aromatase and estrogen receptor alpha in chondrosarcoma, but no beneficial effect of inhibiting estrogen signaling both in vitro and in vivo.

2012-07-31T14:05:33Z

ABSTRACT: BACKGROUND: Chondrosarcomas are malignant cartilage-forming tumors which are highly resistant to conventional chemotherapy and radiotherapy. Estrogen signaling is known to play an important role in proliferation and differentiation of chondrocytes and in growth plate regulation at puberty. Our experiments focus on unraveling the role of estrogen signaling in the regulation of neoplastic ...

Danielle Meijer, Hans Gelderblom, Marcel Karperien, Anne-Marie Cleton-Jansen, Pancras C W Hogendoorn, Judith V M G Bovee (2011) Clin Sarcoma Res 1: 1

Incidence, predictive factors, and prognosis of chondrosarcoma in patients with Ollier disease and Maffucci syndrome: an international multicenter study of 161 patients.

2012-07-31T14:05:33Z

Enchondromatosis is characterized by the presence of multiple benign cartilage lesions in bone. While Ollier disease is typified by multiple enchondromas, in Maffucci syndrome these are associated with hemangiomas. Studies evaluating the predictive value of clinical symptoms for development of secondary chondrosarcoma and prognosis are lacking. This multi-institute study evaluates the clinical cha...

Suzan H M Verdegaal, Judith V M G Bovée, Twinkal C Pansuriya, Robert J Grimer, Harzem Ozger, Paul C Jutte, Mikel San Julian, David J Biau, Ingrid C M van der Geest, Andreas Leithner, Arne Streitbürger, Frank M Klenke, Francois G Gouin, Domenico A Campanacci, Perrine Marec-Berard, Pancras C W Hogendoorn, Ronald Brand, Antonie H M Taminiau (2011) Oncologist 16: 12 1771-1779

Enchondromatosis: insights on the different subtypes.

2011-01-05T07:56:02Z

Enchondromatosis is a rare, heterogeneous skeletal disorder in which patients have multiple enchondromas. Enchondromas are benign hyaline cartilage forming tumors in the medulla of metaphyseal bone. The disorder manifests itself early in childhood without any significant gender bias. Enchondromatosis encompasses several different subtypes of which Ollier disease and Maffucci syndrome are most comm...

Twinkal C Pansuriya, Herman M Kroon, Judith V M G Bovée (2010) Int J Clin Exp Pathol 3: 6 557-569

Cartilage tumours and bone development: molecular pathology and possible therapeutic targets.

2011-01-05T07:56:02Z

As a group, cartilage tumours are the most common primary bone lesions. They range from benign lesions, such as enchondromas and osteochondromas, to malignant chondrosarcoma. The benign lesions result from the deregulation of the hedgehog signalling pathway, which is involved in normal bone development. These lesions can be the precursors of malignant chondrosarcomas, which are notoriously resista...

Judith V M G Bovée, Pancras C W Hogendoorn, Jay S Wunder, Benjamin A Alman (2010) Nat Rev Cancer 10: 7 481-488

No haploinsufficiency but loss of heterozygosity for EXT in multiple osteochondromas.

2011-05-18T14:41:59Z

Multiple osteochondromas (MO) is an autosomal dominant disorder caused by germline mutations in EXT1 and/or EXT2. In contrast, solitary osteochondroma (SO) is nonhereditary. Products of the EXT gene are involved in heparan sulfate (HS) biosynthesis. In this study, we investigated whether osteochondromas arise via either loss of heterozygosity (2 hits) or haploinsufficiency. An in vitro three-dimen...

Christianne M A Reijnders, Cathelijn J F Waaijer, Andrew Hamilton, Emilie P Buddingh, Sander P D Dijkstra, John Ham, Egbert Bakker, Karoly Szuhai, Marcel Karperien, Pancras C W Hogendoorn, Sally E Stringer, Judith V M G Bovée (2010) Am J Pathol 177: 4 1946-1957

Kinome profiling of myxoid liposarcoma reveals NF-kappaB-pathway kinase activity and casein kinase II inhibition as a potential treatment option.

2011-05-18T14:41:59Z

Myxoid liposarcoma is a relatively common malignant soft tissue tumor, characterized by a (12;16) translocation resulting in a FUS-DDIT3 fusion gene playing a pivotal role in its tumorigenesis. Treatment options in patients with inoperable or metastatic myxoid liposarcoma are relatively poor though being developed and new hope is growing.

Stefan M Willems, Yvonne M Schrage, Inge H Briaire-de Bruijn, Karoly Szuhai, Pancras C W Hogendoorn, Judith V M G Bovée (2010) Mol Cancer 9:

Tiling resolution array-CGH shows that somatic mosaic deletion of the EXT gene is causative in EXT gene mutation negative multiple osteochondromas patients.

2012-03-06T21:29:00Z

Matrix biochemistry and cell biology of dedifferentiated chondrosarcomas.

2011-01-05T07:56:02Z

Dedifferentiated chondrosarcoma is an uncommon mesenchymal neoplasm comprised of two different components, low-grade conventional chondrosarcoma and high-grade non-cartilaginous sarcoma. In order to gain better insight into the biology of this tumor, we investigated a large series of dedifferentiated chondrosarcomas by looking at the composition of the extracellular tumor matrix within each of the...

Kerstin Dornauer, Stephan Söder, Carry Y Inwards, Judith V M G Bovee, Thomas Aigner (2010) Pathol Int 60: 5 365-372

Correlation of hypoxic signalling to histological grade and outcome in cartilage tumours.

2011-01-05T07:56:02Z

The molecular mechanisms underlying the progression of central chondrosarcoma are so far poorly understood. The aim of this study was to identify genes involved in the progression of these tumours by comparison of gene expression and correlation of expression profiles to histological grade and clinical outcome.

Stephane Boeuf, Judith V M G Bovée, Burkhard Lehner, Pancras C W Hogendoorn, Wiltrud Richter (2010) Histopathology 56: 5 641-651

Molecular pathology of sarcomas: concepts and clinical implications.

2011-01-05T07:56:52Z

The molecular genetic changes that have been described in sarcomas over the past era have aided our understanding of their pathogenesis. The majority of sarcomas carry nonspecific genetic changes within a background of a complex karyotype. These constitute the challenges in sarcoma research for unraveling a putative multistep genetic model, such as for chondrosarcoma, and finding targets for thera...

Judith V M G Bovée, Pancras C W Hogendoorn (2010) Virchows Arch 456: 2 193-199

Hierarchical clustering of flow cytometry data for the study of conventional central chondrosarcoma.

2011-01-05T07:56:02Z

We have investigated the use of hierarchical clustering of flow cytometry data to classify samples of conventional central chondrosarcoma, a malignant cartilage forming tumor of uncertain cellular origin, according to similarities with surface marker profiles of several known cell types. Human primary chondrosarcoma cells, articular chondrocytes, mesenchymal stem cells, fibroblasts, and a panel of...

Jose Diaz-Romero, Salvatore Romeo, Judith V M G Bovée, Pancras C W Hogendoorn, Paul F Heini, Pierre Mainil-Varlet (2010) J Cell Physiol 225: 2 601-611

COX-2 expression in chondrosarcoma: a role for celecoxib treatment?

2011-01-05T07:56:52Z

Chondrosarcomas are resistant to conventional chemo- and radiotherapy. A subset of chondrosarcomas arises secondarily in the benign tumour syndromes enchondromatosis (EC) and multiple osteochondromas (MO), and prevention of tumour development would greatly improve prognosis. We therefore investigated the effect of selective COX-2 inhibition on chondrosarcoma growth. COX-2 expression was studied in...

Y M Schrage, I Machado, D Meijer, I Briaire-de Bruijn, B E van den Akker, A H M Taminiau, T Kalinski, A Llombart-Bosch, J V M G Bovée (2010) Eur J Cancer 46: 3 616-624

EXTra hit for mouse osteochondroma.

2011-01-05T07:56:52Z

Judith V M G Bovée (2010) Proc Natl Acad Sci U S A 107: 5 1813-1814

Primary cilia organization reflects polarity in the growth plate and implies loss of polarity and mosaicism in osteochondroma.

2011-01-05T07:56:02Z

Primary cilia are specialized cell surface projections found on most cell types. Involved in several signaling pathways, primary cilia have been reported to modulate cell and tissue organization. Although they have been implicated in regulating cartilage and bone growth, little is known about the organization of primary cilia in the growth plate cartilage and osteochondroma. Osteochondromas are bo...

Carlos E de Andrea, Malgorzata Wiweger, Frans Prins, Judith V M G Bovée, Salvatore Romeo, Pancras C W Hogendoorn (2010) Lab Invest 90: 7 1091-1101

A reappraisal of hemangiopericytoma of bone; analysis of cases reclassified as synovial sarcoma and solitary fibrous tumor of bone.

2011-01-05T07:56:52Z

Hemangiopericytoma (HPC) was first described as a neoplasm with distinct morphologic features, presumably composed of pericytes. In soft tissue, it is accepted that most such lesions are solitary fibrous tumors (SFTs), monophasic synovial sarcomas (SSs), or myofibromatoses. It is unclear whether HPC of bone exists. We reviewed 9 primary "HPC" of bone from 4 institutions diagnosed between 1952 and ...

Sofie L J Verbeke, Christopher D M Fletcher, Marco Alberghini, Søren Daugaard, Adrienne M Flanagan, Tim Parratt, Herman M Kroon, Pancras C W Hogendoorn, Judith V M G Bovée (2010) Am J Surg Pathol 34: 6 777-783

Central chondrosarcoma progression is associated with pRb pathway alterations: CDK4 down-regulation and p16 overexpression inhibit cell growth in vitro.

2012-03-06T21:29:00Z

Chondrosarcomas are highly resistant to conventional radiation and chemotherapy, and surgical removal is the only option for curative treatment. Consequently, there is nothing to offer patients with inoperable tumours and metastatic disease. The aim of this study is to investigate genes involved in cell cycle control: CDK4, CDKN2A/p16, cyclin D1, p21, p53, MDM2 and c-MYC, which may point towards n...

Yvonne M Schrage, Suzanne Lam, Aart G Jochemsen, Anne-Marie Cleton-Jansen, Antonie H M Taminiau, Pancras C W Hogendoorn, Judith V M G Bovée (2009) J Cell Mol Med 13: 9A 2843-2852

The molecular and cellular basis of exostosis formation in hereditary multiple exostoses.

2009-09-29T18:06:49Z

Christianne M A Reijnders, Pancras C W Hogendoorn, Judith V M G Bovée (2009) Int J Exp Pathol 90: 2 190-1; author reply 191-3

Assessment of interobserver variability and histologic parameters to improve reliability in classification and grading of central cartilaginous tumors.

2009-09-29T18:06:49Z

The distinction between benign and malignant cartilaginous tumors of bone is one of the most difficult subjects in surgical pathology. The grading of chondrosarcoma also seems to vary considerably among pathologists. However, clinical management differs. The purpose of this study was (1) to investigate interobserver variability in histological diagnosis and grading of central cartilaginous tumors ...

Daniël Eefting, Yvonne M Schrage, Maartje J A Geirnaerdt, Saskia Le Cessie, Anthonie H M Taminiau, Judith V M G Bovée, Pancras C W Hogendoorn (2009) Am J Surg Pathol 33: 1 50-57

Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors.

2009-09-29T18:06:49Z

PURPOSE: Histologic grade is currently the best predictor of clinical course in chondrosarcoma patients. Grading suffers, however, from extensive interobserver variability and new objective markers are needed. Hence, we have investigated DNA copy numbers in chondrosarcomas with the purpose of identifying markers useful for prognosis and subclassification. EXPERIMENTAL DESIGN: The overall pattern o...

Karolin H Hallor, Johan Staaf, Judith V M G Bovée, Pancras C W Hogendoorn, Anne-Marie Cleton-Jansen, Sakari Knuutila, Suvi Savola, Tarja Niini, Otte Brosjö, Henrik C F Bauer, Fredrik Vult von Steyern, Kjell Jonsson, Mikael Skorpil, Nils Mandahl, Fredrik Mertens (2009) Clin Cancer Res 15: 8 2685-2694

Aberrant heparan sulfate proteoglycan localization, despite normal exostosin, in central chondrosarcoma.

2009-09-29T18:06:49Z

The tumor suppressor genes EXT1 and EXT2 are involved in the formation of multiple osteochondromas, which can progress to become secondary peripheral chondrosarcomas. The most common chondrosarcoma subtype is primary central chondrosarcoma, which occurs in the medullar cavity of bone. The EXT1/EXT2 protein complex is involved in heparan sulfate proteoglycan (HSPG) biosynthesis, which is important ...

Yvonne M Schrage, Liesbeth Hameetman, Karoly Szuhai, Anne-Marie Cleton-Jansen, Antonie H M Taminiau, Pancras C W Hogendoorn, Judith V M G Bovée (2009) Am J Pathol 174: 3 979-988

Metastatic potential of an aneurysmal bone cyst.

2011-01-05T07:56:52Z

Aneurysmal bone cysts (ABCs) are benign bone tumors consisting of blood-filled cavities lined by connective tissue septa. Recently, the hypothesis that ABCs are lesions reactive to local hemodynamics has been challenged after the discovery of specific recurrent chromosomal abnormalities. Multiple cases of malignant transformation of ABC into (osteo)sarcoma have been described, as well as a number ...

Addy C M van de Luijtgaarden, Rene P H Veth, Piet J Slootweg, Pauline M Wijers-Koster, Leo J Schultze Kool, Judith V M G Bovee, Winette T A van der Graaf (2009) Virchows Arch 455: 5 455-459

Kinome profiling of chondrosarcoma reveals SRC-pathway activity and dasatinib as option for treatment.

2009-09-29T18:06:49Z

Chondrosarcomas are notorious for their resistance to conventional chemotherapy and radiotherapy, indicating there are no curative treatment possibilities for patients with inoperable or metastatic disease. We therefore explored the existence of molecular targets for systemic treatment of chondrosarcoma using kinome profiling. Peptide array was performed for four chondrosarcoma cell lines and nine...

Yvonne M Schrage, Inge H Briaire-de Bruijn, Noel F C C de Miranda, Jolieke van Oosterwijk, Antonie H M Taminiau, Tom van Wezel, Pancras C W Hogendoorn, Judith V M G Bovée (2009) Cancer Res 69: 15 6216-6222

Dedifferentiated peripheral chondrosarcomas: regulation of EXT-downstream molecules and differentiation-related genes.

2012-03-06T21:29:00Z

Dedifferentiated peripheral chondrosarcoma is a rare subtype of chondrosarcoma arising superimposed on the cartilage cap of a preexisting osteochondroma. It consists of two clearly defined components, a low-grade malignant, well-differentiated cartilage component and a high-grade non-cartilaginous sarcoma. Signaling pathways having a role in normal cartilage development were analyzed in these tumo...

Leida B Rozeman, Inge H Briaire de Bruijn, Patrizia Bacchini, Eric L Staals, Franco Bertoni, Judith V M G Bovée, Pancras Cw Hogendoorn (2009) Mod Pathol 22: 11 1489-1498

Extra-abdominal subcutaneous metastasis of a gastrointestinal stromal tumor: report of a case and a review of the literature.

2009-09-29T18:06:49Z

Gastrointestinal stromal tumors (GISTs) metastasize primarily within the peritoneal cavity and to the liver. Superficial soft tissue metastases occur in about 1% of advanced GIST and are mostly associated with abdominal laparotomy scars and advanced disease. Extra-abdominal subcutaneous metastases of GIST have not been previously reported. Subcutaneous spindle cell tumors constitute a diagnostic c...

Judith R Kroep, Judith V M G Bovée, Aart J van der Molen, Pancras C W Hogendoorn, Hans Gelderblom (2009) J Cutan Pathol 36: 5 565-569

A chondrogenic gene expression signature in mesenchymal stem cells is a classifier of conventional central chondrosarcoma.

2009-09-29T18:07:59Z

Phenotypic and molecular parallels between the development of chondrosarcoma and the differentiation of chondrocytes in normal growth plate suggest that chondrosarcoma may arise from mesenchymal precursor cells driven towards chondrogenesis. We hypothesized that a comparison between cartilaginous tumours and their possible physiological cells of origin, mesenchymal stem cells (MSCs), might have bi...

S Boeuf, P Kunz, T Hennig, B Lehner, Pcw Hogendoorn, Jvmg Bovée, W Richter (2008) J Pathol 216: 2 158-166

Osteosarcoma of the femur with skip, lymph node, and lung metastases.

2009-09-29T18:06:49Z

Tjeerd Zwaga, Judith V M G Bovée, Herman M Kroon (2008) Radiographics 28: 1 277-283

Myxoid tumours of soft tissue: the so-called myxoid extracellular matrix is heterogeneous in composition.

2009-09-29T18:06:49Z

AIM: Myxoid tumours of soft tissue are characterized by their so-called 'myxoid' extracellular matrix. The aim was to investigate the composition and possible function of this matrix which is poorly understood. METHODS AND RESULTS: Using Alcian Blue staining with and without pretreatment with hyaluronidase and application of the critical electrolyte concentration method followed by densitometry, t...

S M Willems, Y M Schrage, J J Baelde, I Briaire-de Bruijn, A Mohseny, R Sciot, J V M G Bovée, P C W Hogendoorn (2008) Histopathology 52: 4 465-474

Multiple osteochondromas.

2009-09-29T18:06:49Z

Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones. The prevalence is estimated at 1:50,000, and it seems to be higher in males (male-to-female ratio 1.5:1). Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. They are peduncu...

Judith V M G Bovée (2008) Orphanet J Rare Dis 3:

The clinical approach towards chondrosarcoma.

2009-09-29T18:06:49Z

This review provides an overview of the histopathology, classification, diagnostic procedures, and therapy of skeletal chondrosarcoma. Chondrosarcomas that arise de novo are primary chondrosarcomas, whereas chondrosarcomas developing superimposed on pre-existing benign cartilage neoplasms such as enchondromas or osteochondromas are referred to as secondary chondrosarcomas. Conventional chondrosarc...

Hans Gelderblom, Pancras C W Hogendoorn, Sander D Dijkstra, Carla S van Rijswijk, Augustinus D Krol, Antonie H M Taminiau, Judith V M G Bovée (2008) Oncologist 13: 3 320-329

Decreased EXT expression and intracellular accumulation of heparan sulphate proteoglycan in osteochondromas and peripheral chondrosarcomas.

2009-09-29T18:06:49Z

Mutational inactivation of EXT1 or EXT2 is the cause of hereditary multiple osteochondromas. These genes function in heparan sulphate proteoglycan (HSPG) biosynthesis in the Golgi apparatus. Loss of heterozygosity of the EXT1 locus at 8q24 is frequently found in solitary osteochondromas, whereas somatic mutations are rarely found. We investigated the expression of EXT1 and EXT2 (quantitative RT-PC...

L Hameetman, G David, A Yavas, S J White, A H M Taminiau, A-M Cleton-Jansen, P C W Hogendoorn, J V M G Bovée (2007) J Pathol 211: 4 399-409

The role of noncartilage-specific molecules in differentiation of cartilaginous tumors: lessons from chondroblastoma and chondromyxoid fibroma.

2009-09-29T18:06:49Z

BACKGROUND: Chondroblastoma (CB) and chondromyxoid fibroma (CMF) are benign tumors of bone morphologically recapitulating cartilage differentiation. CMF can resemble high-grade central chondrosarcoma (HGCCS) because of its cellular atypia. The mechanism that drives this morphologic spectrum of cartilage differentiation is unclear. METHODS: CMFs and CBs were hybridized on a complementary DNA microa...

Salvatore Romeo, Jan Oosting, Leida B Rozeman, Liesbeth Hameetman, Antonie H M Taminiau, Anne Marie Cleton-Jansen, Judith V M G Bovée, Pancras C W Hogendoorn (2007) Cancer 110: 2 385-394

The role of EXT1 in nonhereditary osteochondroma: identification of homozygous deletions.

2009-09-29T18:06:49Z

BACKGROUND: Multiple osteochondromas is a hereditary syndrome that is characterized by the formation of cartilage-capped bony neoplasms (osteochondromas), for which exostosis (multiple)-1 (EXT1) has been identified as a causative gene. However, 85% of all osteochondromas present as solitary (nonhereditary) lesions in which somatic mutations in EXT1 are extremely rare, but loss of heterozygosity an...

Liesbeth Hameetman, Karoly Szuhai, Ayse Yavas, Jeroen Knijnenburg, Mark van Duin, Herman van Dekken, Antonie H M Taminiau, Anne-Marie Cleton-Jansen, Judith V M G Bovée, Pancras C W Hogendoorn (2007) J Natl Cancer Inst 99: 5 396-406

CT-guided, COBRA-FISH-assisted diagnosis of well-differentiated liposarcoma (inflammatory subtype) of the retroperitoneum.

2009-09-29T18:06:49Z

S M Willems, K Szuhai, H Hartgrink, J V M G Bovée, A De Schepper, P C W Hogendoorn (2007) Histopathology 51: 3 422-426

EXT-related pathways are not involved in the pathogenesis of dysplasia epiphysealis hemimelica and metachondromatosis.

2009-09-29T18:06:49Z

Dysplasia epiphysealis hemimelica (DEH) and metachondromatosis (MC) are considered in the differential diagnosis of solitary and hereditary osteochondromas. Both are rare disorders with DEH demonstrating cartilaginous overgrowth of an epiphysis and MC exhibiting synchronous enchondromas and osteochondromas. Ten cases of DEH and two of MC were compared with osteochondromas at the histological and m...

J V M G Bovée, L Hameetman, H M Kroon, T Aigner, P C W Hogendoorn (2006) J Pathol 209: 3 411-419

Peripheral chondrosarcoma progression is accompanied by decreased Indian Hedgehog signalling.

2009-09-29T18:06:49Z

Hedgehog (HH) signalling is important for specific developmental processes, and aberrant, increased activity has been described in various tumours. Disturbed HH signalling has also been implicated in the hereditary syndrome, Multiple Osteochondromas. Indian Hedgehog (IHH), together with parathyroid hormone-like hormone (PTHLH), participates in the organization of growth plates in long bones. PTHLH...

L Hameetman, L B Rozeman, M Lombaerts, J Oosting, A H M Taminiau, A-M Cleton-Jansen, J V M G Bovée, P C W Hogendoorn (2006) J Pathol 209: 4 501-511

Array-comparative genomic hybridization of central chondrosarcoma: identification of ribosomal protein S6 and cyclin-dependent kinase 4 as candidate target genes for genomic aberrations.

2009-09-29T18:06:49Z

BACKGROUND: Enchondromas are benign lesions that can occur as solitary tumors or multiple tumors (Ollier disease) and may be precursors of central chondrosarcomas. Recurrent chondrosarcomas can be of a higher grade compared with primary tumors, suggesting possible progression. METHODS: Genome-wide array-comparative genomic hybridization (CGH) was used to investigate copy number changes in enchondr...

Leida B Rozeman, Karoly Szuhai, Yvonne M Schrage, Carla Rosenberg, Hans J Tanke, Antonie H M Taminiau, Anne Marie Cleton-Jansen, Judith V M G Bovée, Pancras C W Hogendoorn (2006) Cancer 107: 2 380-388

Estrogen signaling is active in cartilaginous tumors: implications for antiestrogen therapy as treatment option of metastasized or irresectable chondrosarcoma.

2009-09-29T18:06:49Z

PURPOSE: Chondrosarcoma is a malignant cartilaginous matrix-producing tumor that can be lethal in 10% to 50% of the patients. Surgery is the only effective treatment known as these tumors are notorious refractory to all types of conventional chemotherapy or radiotherapy. To identify a target for therapy, we want to determine whether estrogen signaling is active in chondrosarcoma because estrogen i...

Anne-Marie Cleton-Jansen, Hetty M van Beerendonk, Hans J Baelde, Judith V G M Bovée, Marcel Karperien, Pancras C W Hogendoorn (2005) Clin Cancer Res 11: 22 8028-8035

Chondromyxoid fibroma resembles in vitro chondrogenesis, but differs in expression of signalling molecules.

2009-09-29T18:06:49Z

Chondromyxoid fibroma is a rare benign cartilaginous bone tumour characterized by morphological features that resemble different steps of chondrogenesis in terms of both cellular morphology, ranging from spindled to rounded cells, and the extracellular matrix formed, which ranges from fibrous to cartilaginous. The presence in chondromyxoid fibroma of signalling molecules that regulate the spatial ...

Salvatore Romeo, Judith V M G Bovée, Shawn P Grogan, Antonie H M Taminiau, Paul H C Eilers, Anne Marie Cleton-Jansen, Pierre Mainil-Varlet, Pancras C W Hogendoorn (2005) J Pathol 206: 2 135-142

Absence of IHH and retention of PTHrP signalling in enchondromas and central chondrosarcomas.

2009-09-29T18:06:49Z

Enchondromas and conventional central chondrosarcomas are, respectively, benign and malignant hyaline cartilage-forming tumours that originate in the medulla of bone. In order to gain a better understanding of the molecular process underlying malignant transformation of enchondroma, and to investigate whether there is a biological difference between conventional central cartilaginous tumours and t...

Leida B Rozeman, Liesbeth Hameetman, Anne-Marie Cleton-Jansen, Anthonie H M Taminiau, Pancras C W Hogendoorn, Judith V M G Bovée (2005) J Pathol 205: 4 476-482

cDNA expression profiling of chondrosarcomas: Ollier disease resembles solitary tumours and alteration in genes coding for components of energy metabolism occurs with increasing grade.

2009-09-29T18:06:49Z

Conventional central chondrosarcomas are malignant cartilaginous tumours, occasionally arising secondary to either solitary or multiple (Ollier disease) enchondromas. Recurrences may have progressed in grade. The aims of the present study were to identify putative differences in gene expression between solitary and Ollier disease-related tumours, and to elucidate signalling pathways involved in tu...

Leida B Rozeman, Liesbeth Hameetman, Tom van Wezel, Antonie H M Taminiau, Anne Marie Cleton-Jansen, Pancras C W Hogendoorn, Judith V M G Bovée (2005) J Pathol 207: 1 61-71

The use of Bcl-2 and PTHLH immunohistochemistry in the diagnosis of peripheral chondrosarcoma in a clinicopathological setting.

2009-09-29T18:06:49Z

Distinguishing osteochondroma from low-grade secondary peripheral chondrosarcoma can be difficult. In osteochondroma, growth-signalling pathways are thought to be downregulated through exostosin (EXT) inactivation. A previous pilot study focusing on expression of putative EXT downstream effectors indicated that progression of osteochondroma towards grade I chondrosarcoma was characterised by upreg...

Liesbeth Hameetman, Petra Kok, Paul H C Eilers, Anne-Marie Cleton-Jansen, Pancras C W Hogendoorn, Judith V M G Bovée (2005) Virchows Arch 446: 4 430-437

Emerging pathways in the development of chondrosarcoma of bone and implications for targeted treatment.

2009-09-29T18:06:49Z

Chondrosarcoma is a malignant cartilage-forming tumour of bone, of which distinct clinicopathological subtypes are known. Conventional chondrosarcoma is notorious for its locally aggressive behaviour as well as for its resistance to chemotherapy and radiotherapy; so far surgery is the only effective therapeutic option. During the past 10 years, substantial new insights have been gained about molec...

Judith V M G Bovée, Anne-Marie Cleton-Jansen, Antonie H M Taminiau, Pancras C W Hogendoorn (2005) Lancet Oncol 6: 8 599-607

Pitfalls in pathology of soft tissue sarcomas.

2009-09-29T18:06:49Z

Judith V M G Bovée, Pancras C W Hogendoorn (2004) Cancer Treat Res 120: 81-97

Expression of cartilage growth plate signalling molecules in chondroblastoma.

2009-09-29T18:06:49Z

Chondroblastoma (CB) is a rare benign tumour (<1% of all bone tumours) involving epiphyseal long bones (male:female 1.5:1). During development, and in the postnatal period, IHh/PTHrP and FGF signalling molecules control the space and timing of chondrocyte differentiation. Considering the close relationship of CB with the growth plate (age and location), the expression of proteins involved in epiph...

S Romeo, J V M G Bovée, N A A Jadnanansing, A H M Taminiau, P C W Hogendoorn (2004) J Pathol 202: 1 113-120

Molecular analysis of the INK4A/INK4A-ARF gene locus in conventional (central) chondrosarcomas and enchondromas: indication of an important gene for tumour progression.

2009-09-29T18:06:49Z

Loss of heterozygosity (LOH) at chromosomal band 9p21 is one of the few consistent genetic aberrations found in conventional chondrosarcoma. This locus harbours two cell-cycle regulators, CDKN2A/p16/INK4A and INK4A-p14ARF, which are inactivated in various human malignancies. It was therefore hypothesized that this locus also plays a role in the development of chondrosarcoma and this locus was inve...

Hetty M van Beerendonk, Leida B Rozeman, Antonie H M Taminiau, Raf Sciot, Judith V M G Bovée, Anne-Marie Cleton-Jansen, Pancras C W Hogendoorn (2004) J Pathol 202: 3 359-366

Enchondromatosis (Ollier disease, Maffucci syndrome) is not caused by the PTHR1 mutation p.R150C.

2009-09-29T18:06:49Z

Enchondromatosis (Ollier disease, Maffucci syndrome) is a rare developmental disorder characterized by multiple enchondromas. Not much is known about its molecular genetic background. Recently, an activating mutation in the parathyroid hormone receptor type 1 (PTHR1) gene, c.448C>T (p.R150C), was reported in two of six patients with enchondromatosis. The mutation is thought to result in upregulati...

Leida B Rozeman, Luca Sangiorgi, Inge H Briaire-de Bruijn, Pierre Mainil-Varlet, F Bertoni, Anne Marie Cleton-Jansen, Pancras C W Hogendoorn, Judith V M G Bovée (2004) Hum Mutat 24: 6 466-473

Epigenetic loss of the familial tumor-suppressor gene exostosin-1 (EXT1) disrupts heparan sulfate synthesis in cancer cells.

2009-09-29T18:09:43Z

Germline mutations in the Exostoses-1 gene (EXT1) are found in hereditary multiple exostoses syndrome, which is characterized by the formation of osteochondromas and an increased risk of chondrosarcomas and osteosarcomas. However, despite its putative tumor-suppressor function, little is known of the contribution of EXT1 to human sporadic malignancies. Here, we report that EXT1 function is abrogat...

Santiago Ropero, Fernando Setien, Jesus Espada, Mario F Fraga, Michel Herranz, Julia Asp, Maria Serena Benassi, Alessandro Franchi, Ana Patiño, Laura S Ward, Judith Bovee, Juan C Cigudosa, Wuyts Wim, Manel Esteller (2004) Hum Mol Genet 13: 22 2753-2765

From gene to disease; hereditary multiple exostoses

2009-09-29T18:06:49Z

Hereditary multiple exostoses is an autosomal dominant disorder characterised by the presence of multiple osteochondromas, resulting in a variety of skeletal deformities. It is a genetically heterogeneous condition for which two genes, EXT1 and EXT2, have been isolated. The EXT1 gene, located at 8q24, has been shown to harbour mutations in 44-66% of the hereditary multiple exostoses-families. Muta...

W Wuyts, J V M G Bovée, P C W Hogendoorn (2002) Ned Tijdschr Geneeskd 146: 4 162-164

Diagnosis and prognosis of chondrosarcoma of bone.

2009-09-29T18:06:49Z

The mechanisms of chondrosarcoma development are just beginning to be unraveled. The distinction between benign and low-grade malignant cartilaginous tumors is difficult and is based mainly on radiological and clinicopathological features. In this review, the conventional chondrosarcomas are subdivided into central and secondary peripheral chondrosarcomas, based on their different genetic and clin...

Leida B Rozeman, Pancras C W Hogendoorn, Judith V M G Bovée (2002) Expert Rev Mol Diagn 2: 5 461-472

Intermediate grade osteosarcoma and chondrosarcoma arising in an osteochondroma. A case report of a patient with hereditary multiple exostoses.

2009-09-29T18:06:49Z

A 40 year old man with hereditary multiple exostoses (HME), affecting predominantly his left proximal tibia, distal femur, and proximal femur, underwent resection of an osteochondroma near the trochanter major of his left proximal femur because of malignant transformation of the cartilaginous cap towards secondary peripheral chondrosarcoma. The patient had a history of a papillary thyroid carcinom...

J V M G Bovée, R J B Sakkers, M J A Geirnaerdt, A H M Taminiau, P C W Hogendoorn (2002) J Clin Pathol 55: 3 226-229

Chromosome 9 alterations and trisomy 22 in central chondrosarcoma: a cytogenetic and DNA flow cytometric analysis of chondrosarcoma subtypes.

2009-09-29T18:06:49Z

Chondrosarcomas are malignant cartilaginous tumors. Most are located in the medullar cavity (central chondrosarcoma), and a minority develop in a preexisting osteochondroma (peripheral chondrosarcoma). The authors present karyotypes for 37 central, peripheral, juxtacortical, and dedifferentiated chondrosarcomas. Using loss of heterozygosity (LOH) analysis and DNA flow cytometry, the authors previo...

J V Bovée, R Sciot, P Dal Cin, M Debiec-Rychter, S L van Zelderen-Bhola, C J Cornelisse, P C Hogendoorn (2001) Diagn Mol Pathol 10: 4 228-235

Chondrosarcoma is not characterized by detectable telomerase activity.

2009-09-29T18:06:49Z

Reactivation of telomerase, an enzyme which elongates human telomeres, is associated with cell immortilization. In approximately 90% of malignant tumours telomerase activity can be demonstrated, whereas in benign tumours it is mostly absent. Chondrosarcomas are relatively rare malignant cartilaginous neoplasms. A small number of chondrosarcomas located centrally in bone arise secondarily to an enc...

J V Bovée, L J van Den Broek, A M Cleton-Jansen, P C Hogendoorn (2001) J Pathol 193: 3 354-360

High quality RNA isolation from tumours with low cellularity and high extracellular matrix component for cDNA microarrays: application to chondrosarcoma.

2009-09-29T18:06:49Z

AIMS: High quality RNA isolation from cartilaginous tissue is considered difficult because of relatively low cellularity and the abundance of extracellular matrix rich in glycosaminoglycans and collagens. Given the growing interest and technical possibilities to study RNA expression at a high throughput level, research on tissue with these characteristics is hampered by the lack of an efficient me...

H J Baelde, A M Cleton-Jansen, H van Beerendonk, M Namba, J V Bovée, P C Hogendoorn (2001) J Clin Pathol 54: 10 778-782

An update of diagnostic strategies using molecular genetic and magnetic resonance imaging techniques for musculoskeletal tumors.

2009-09-29T18:06:49Z

Rheumatologists may be incidentally confronted by bone and soft tissue lesions presenting in and around joints that require early recognition and appropriate referral. The diagnostic and therapeutic management of patients with musculoskeletal tumors is critically dependent on a multidisciplinary approach. Advances, particularly in the fields of histopathology, molecular (cyto)genetics and radiolog...

J F Graadt van Roggen, J V Bovée, H J van der Woude, P C Hogendoorn (2000) Curr Opin Rheumatol 12: 1 77-83

Up-regulation of PTHrP and Bcl-2 expression characterizes the progression of osteochondroma towards peripheral chondrosarcoma and is a late event in central chondrosarcoma.

2009-09-29T18:06:49Z

Chondrosarcomas are malignant cartilage-forming tumors arising centrally in bone (central chondrosarcoma) or within the cartilaginous cap of osteochondroma (peripheral chondrosarcoma). For hereditary multiple osteochondromas, two responsible genes, EXT1 and EXT2, have been cloned. Their recently elucidated role in heparan sulfate biosynthesis and Hedgehog diffusion leads to the hypothesis that EXT...

J V Bovée, L J van den Broek, A M Cleton-Jansen, P C Hogendoorn (2000) Lab Invest 80: 12 1925-1934

Near-haploidy and subsequent polyploidization characterize the progression of peripheral chondrosarcoma.

2009-09-29T18:06:49Z

Chondrosarcomas are malignant cartilaginous tumors arising centrally in bone (central chondrosarcoma), or secondarily within the cartilaginous cap of osteochondroma (peripheral chondrosarcoma). We previously used DNA flow cytometry to demonstrate that near-haploidy is relatively frequent in peripheral chondrosarcomas. We performed fluorescence in situ hybridization (FISH) to interphase nuclei usin...

J V Bovée, M van Royen, A F Bardoel, C Rosenberg, C J Cornelisse, A M Cleton-Jansen, P C Hogendoorn (2000) Am J Pathol 157: 5 1587-1595

Malignant progression in multiple enchondromatosis (Ollier's disease): an autopsy-based molecular genetic study.

2009-09-29T18:06:49Z

Multiple enchondromatosis (Ollier's disease) is a nonhereditary disease characterized by multiple central (medullary) cartilaginous bone tumors of unknown pathogenesis. It usually involves the extremities with a unilateral predominance, and sarcomatous transformation may occur. We report an autopsy-based genetic study of a 34-year-old man presenting in early adolescence with multiple enchondromas ...

J V Bovée, J F van Roggen, A M Cleton-Jansen, A H Taminiau, H J van der Woude, P C Hogendoorn (2000) Hum Pathol 31: 10 1299-1303

Re. Review article entitled 'The neoplastic pathogenesis of solitary and multiple osteochondromas'.

2009-09-29T18:06:49Z

J V Bovée, P C Hogendoorn (2000) J Pathol 190: 4 516-517

Chondrosarcoma of the phalanx: a locally aggressive lesion with minimal metastatic potential: a report of 35 cases and a review of the literature.

2009-09-29T18:06:49Z

BACKGROUND: Enchondroma is the most common primary benign bone tumor of the hand, especially the phalanges, whereas chondrosarcoma is uncommon at this site. Although phalangeal chondrosarcoma may have ominous histologic features, its biologic behavior is relatively indolent. METHODS: Thirty-five cases of phalangeal lesions previously diagnosed as chondrosarcoma were studied. Histologic and tumor-b...

J V Bovée, R O van der Heul, A H Taminiau, P C Hogendoorn (1999) Cancer 86: 9 1724-1732

Molecular genetic characterization of both components of a dedifferentiated chondrosarcoma, with implications for its histogenesis.

2009-09-29T18:06:49Z

Dedifferentiated chondrosarcoma is defined as a high-grade, anaplastic sarcoma adjacent to a low-grade malignant cartilage-forming tumour. Controversy remains as to whether the anaplastic and cartilaginous components are derived from a common precursor cell, or whether they represent separate genotypic lineages (collision tumour). Both components of a case of dedifferentiated chondrosarcoma were t...

J V Bovée, A M Cleton-Jansen, C Rosenberg, A H Taminiau, C J Cornelisse, P C Hogendoorn (1999) J Pathol 189: 4 454-462

Diagnostic and prognostic implications of the unfolding molecular biology of bone and soft tissue tumours.

2009-09-29T18:06:49Z

Sarcomas account for approximately 1-2% of human malignant disease and are relatively uncommon. Histopathological study of these mesenchymal tumours at light microscopic and ultrastructural level may not always provide an unambiguous diagnosis. It has become apparent with the identification of increasing numbers of tumour specific genetic alterations that (cyto) genetic evaluation could become a v...

J F Graadt van Roggen, J V Bovée, J Morreau, P C Hogendoorn (1999) J Clin Pathol 52: 7 481-489

Loss of heterozygosity and DNA ploidy point to a diverging genetic mechanism in the origin of peripheral and central chondrosarcoma.

2009-09-29T18:06:49Z

Chondrosarcomas are malignant cartilaginous tumors arising centrally in bone (central chondrosarcoma), or secondarily within the cartilaginous cap of a hereditary or sporadic exostosis (peripheral chondrosarcoma). Loss of heterozygosity (LOH) was studied by microsatellite analysis at the loci harboring the EXT genes (implicated in hereditary multiple exostoses), the EXT-like genes, and at 9p21, 13...

J V Bovée, A M Cleton-Jansen, N J Kuipers-Dijkshoorn, L J van den Broek, A H Taminiau, C J Cornelisse, P C Hogendoorn (1999) Genes Chromosomes Cancer 26: 3 237-246

EXT-mutation analysis and loss of heterozygosity in sporadic and hereditary osteochondromas and secondary chondrosarcomas.

2009-09-29T18:06:49Z

Osteochondromas occur as sporadic solitary lesions or as multiple lesions, characterizing the hereditary multiple exostoses syndrome (EXT). Approximately 15% of all chondrosarcomas arise within the cartilaginous cap of an osteochondroma. EXT is genetically heterogeneous, and two genes, EXT1 and EXT2, located on 8q24 and 11p11-p12, respectively, have been cloned. It is still unclear whether osteoch...

J V Bovée, A M Cleton-Jansen, W Wuyts, G Caethoven, A H Taminiau, E Bakker, W Van Hul, C J Cornelisse, P C Hogendoorn (1999) Am J Hum Genet 65: 3 689-698

Ring chromosome 4 as the sole cytogenetic anomaly in a chondroblastoma: a case report and review of the literature.

2009-09-29T18:06:49Z

Chromosome analysis of a chondroblastoma of the right distal femur in a 31-year-old male patient revealed a ring chromosome 4 in approximately one-third of the analyzed cells. The remaining cells had a normal karyotype. These findings were subsequently confirmed by fluorescence in situ hybridization (FISH) with a chromosome-4-specific library. FISH with cosmids pC847.351 (4p16.3) and cT171 (4q35) ...

S L van Zelderen-Bhola, J V Bovée, H W Wessels, P Mollevanger, J V Nijhuis, J D van Eendenburg, A H Taminiau, P C Hogendoorn (1998) Cancer Genet Cytogenet 105: 2 109-112

Expression of growth factors and their receptors in adamantinoma of long bones and the implication for its histogenesis.

2009-09-29T18:06:49Z

Adamantinoma of long bones is a rare bone tumour with (immuno-) histological features of epithelial cells, surrounded by various amounts of osteofibrous tissue. Recent studies have indicated that cells with an epithelial phenotype are most probably the malignant element. There is still debate as to whether the fibrous part should be designed as a benign neoplastic element of a biphasic tumour or a...

J V Bovée, L J van den Broek, W I de Boer, P C Hogendoorn (1998) J Pathol 184: 1 24-30

Molecular biology diagnosis of tumors of the musculoskeletal system

2009-09-29T18:06:49Z

It is sometimes difficult to make an unequivocal diagnosis of tumours of bone and soft tissue based upon classical morphology alone, which has led to an increased use of additional diagnostic tools. In the past decade new techniques have become available, based on tumour specific genetic alterations, for instance chromosomal translocations. With the cloning of the translocation breakpoints and the...

J V Bovée, P C Hogendoorn (1997) Ned Tijdschr Geneeskd 141: 52 2557-2562

Deletions of the long arm of chromosome 10 in progression of follicular thyroid tumors.

2009-09-29T18:09:43Z

Previous studies of follicular thyroid tumors have shown loss of heterozygosity (LOH) on the short arm of chromosome 3 in carcinomas, and on chromosome 10 in atypical adenomas and carcinomas, but not in common adenomas. We studied LOH on these chromosomal arms in 15 follicular thyroid carcinomas, 19 atypical follicular adenomas and 6 anaplastic (undifferentiated) carcinomas. Deletion mapping of ch...

J Zedenius, G Wallin, A Svensson, J Bovèe, A Höög, M Bäckdahl, C Larsson (1996) Hum Genet 97: 3 299-303

Mutations of codon 918 in the RET proto-oncogene correlate to poor prognosis in sporadic medullary thyroid carcinomas.

2009-09-29T18:09:43Z

The hereditary multiple endocrine neoplasia syndromes types 2A and B (MEN 2A and B) were recently linked to germline mutations in the RET proto-oncogene, altering one of five cysteine residues in exon 10 or 11 (MEN 2A), or substituting a methionine for a threonine at codon 918 in exon 16 (MEN 2B). The latter mutation also occurs somatically in some sporadic medullary thyroid carcinomas (MTC), and ...

J Zedenius, C Larsson, U Bergholm, J Bovée, A Svensson, B Hallengren, L Grimelius, M Bäckdahl, G Weber, G Wallin (1995) J Clin Endocrinol Metab 80: 10 3088-3090

Identification of an EWS-pseudogene using translocation detection by RT-PCR in Ewing's sarcoma.

2009-09-29T18:06:49Z

The presence of a t(11;22)(q24;q12) translocation is one of the characteristic features of the Ewing family of tumors. The detection of the fusion gene product by RT-PCR using primers at both sides of the breakpoints has been advocated as a diagnostic tool. By applying this technique appropriate internal controls are required. We found that the use of normal non-rearranged EWS mRNA as an internal ...

J V Bovée, P Devilee, C J Cornelisse, E Schuuring, P C Hogendoorn (1995) Biochem Biophys Res Commun 213: 3 1051-1060