Mutation of p53 with loss of heterozygosity in the osteosarcomatous component of a dedifferentiated chondrosarcoma

Grote, H.; Schneider‐Stock, Regine; Neumann, Wolfram; Roessner, Albert

doi:10.1007/s004280050478

Cited by 36 publications

(26 citation statements)

References 19 publications

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“…Recent genetic analyses revealed that p53 mutations were detected exclusively in dedifferentiated components. These evidences of a p53 mutation in the dedifferentiated component may be regarded as at least a cofactor that switched the pre-existing low-grade chondrosarcoma to a highly malignant dedifferentiated tumor [20,43,45,53].…”

Section: Discussionmentioning

confidence: 96%

“…There is increasing evidence that tumor suppressor gene mutations play a major role in the development, progression, and /or differentiation of tumors, with p53 mutations occurring frequently in the oncogenesis of various mesenchymal neoplasms [1,2,6,7,13,20,57,60,62]. This cell line has a p53 point mutation (exon 7,codon 242 [Cys→Ser]…”

Section: Discussionmentioning

confidence: 99%

“…The tumor cells (1×10 7 cells suspended in 0.2 ml RPIM; the passage number was 20) were subcutaneously implanted into the mice. Three months after the tumor cell inoculation, the mice were killed, and a specimen was obtained.…”

Section: Establishment Of Cell Linementioning

confidence: 99%

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Establishment of novel human dedifferentiated chondrosarcoma cell line with osteoblastic differentiation

et al. 2007

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Dedifferentiated chondrosarcoma is a rare, highly malignant variant of chondrosarcoma in which a high-grade sarcoma coexists with a low-grade chondroid tumor. We herein review a case of dedifferentiated chondrosarcoma with an osteosarcoma omit component that occurred in the distal femur of a 38-year-old man. We established the cell line (NDCS-1) from a pleural effusion of the metastatic lung tumor. The cell line was characterized by a the G-banded karyotype, polymerase chain reaction (PCR) single-strand conformation polymorphism analysis, spectral karyotyping, and reverse transcriptase PCR (RT-PCR). The tumor exhibited complex karyotypes and a high frequency of chromosomal amplication with p53 mutation. This tumor revealed an osteoblastic and chondroblastic character in vitro and in severe combined immunodeficiency mice. The expression and phosphorylation of platelet-derived growth factor receptor-beta, which seemed to play a major role in the malignant phenotype of chondrosarcoma, was confirmed by RT-PCR and Western blotting. To our knowledge, this is the first report of the establishment of a human dedifferentiated chondrosarcoma.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Establishment of novel human dedifferentiated chondrosarcoma cell line with osteoblastic differentiation

et al. 2007

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“…Strong nuclear immunostaining has been observed in the highgrade non-cartilaginous component, but not in the lowgrade cartilaginous one [8][9][10]. In addition, point mutations of the p53 gene have been identified in the high-grade component of central DCS, and this has also been associated with LOH at 17p [8,[10][11][12]. In one case, a p53 mutation consisting of a 6-bp deletion starting at the second base of codon 250 in exon 7 was detected in both the cartilaginous and the anaplastic components [11].…”

Section: Discussionmentioning

confidence: 99%

Dedifferentiated peripheral chondrosarcoma: a clinicopathologic, immunohistochemical, and molecular analysis of four cases

et al. 2012

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Peripheral dedifferentiated chondrosarcoma (DCS) is an exceedingly rare aggressive surface bone neoplasm in which a high-grade sarcoma arises within an osteochondroma. Four such examples were identified in our files, representing 11.1% of all DCS treated at our hospital in the years 1995-2010, and were the object of the present study. The patients were two men and two women ranging in age between 30 and 64 years, with tumors located in the pelvis (n 0 2), in the scapula (n 0 1), and the tibia (n 0 1). Radiologically, there was evidence of a preexisting osteochondroma associated with aggressive osteolytic areas at the base and periphery of the exostosis, extending to the bone segment of origin and to the soft tissues. Immunohistochemical analysis of cell cycle regulators showed consistent loss in the expression of p16 and overexpression of cyclin D1, and to a lesser extent of RB and p53, in the anaplastic compartments of peripheral DCS in comparison with the well-differentiated cartilaginous components, while no significant expression of MDM2 was observed in any of the cases studied. Moreover, PDGFR! was absent in both tumor components, and PDGF-R" was strongly and diffusely positive in all the cases. Finally, no mutations were identified in exons 4-9 of the TP53 gene in both cases, showing positivity for p53 in the anaplastic component. In conclusion, our study shows that alterations of genes implicated in the regulation of the G1 to the S phase cell cycle checkpoint contribute to the process of dedifferentiation in peripheral secondary chondrosarcoma (CS), although the molecular mechanisms seem at least in part to differ from those involved in the process of dedifferentiation of central CS. PDGFR" could represent a potential target for treatments with receptor tyrosine kinase inhibitors in peripheral DCS.

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“…There is increasing evidence that the tumor suppressor gene mutations play a major role in the development, progression, and/or differentiation of tumors, with p53 mutations and occurring frequently in the oncogenesis of various mesenchymal neoplasms (19)(20)(21)(22)(23). MS0812, in this case, did not show immunoreactivity for p53, the reason for this needs further study.…”

Section: Discussionmentioning

confidence: 70%

A novel mutated cell line with characteristics of dedifferentiated chondrosarcoma

Yang

Chen²,

Zhang³

et al. 2009

Int J Mol Med

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Abstract. Dedifferentiated chondrosarcoma (CS) is a rare, highly malignant variant of CS in which a high-grade sarcoma coexists with a low-grade chondroid tumor. In this study, a novel dedifferentiated CS cell line, MS0812, was spontaneously established from mutated human embryonic muscle cells. Several features of the cell line were investigated, including growth characteristics, cytogenetics, electron microscopic features, expression of various antigenic markers and tumor formation. MS0812 has been cultured continuously for more than 3 years. The growth characteristics of MS0812 are similar to the immortalized cell lines as reported. The cell line exhibited complex karyotypes and hyperploidy, the chromosome number ranged from 50 to 158. MS0812 was positive for vimentin, desmin and muscle actin, indicating their muscle origin. With specific inductive condition, MS0812 differentiates into neural cells and adipocytes. Deletion of the p16 gene, which seemed to play a major role in the malignant phenotype of this cell line, was confirmed by PCR and immunocytochemistry. MS0812 formed tumors in nude mice, and the tumor revealed a fibrosarcoma with chondroid components, which were consistent with dedifferentiated CS as reported. Chondroid components showed metachromasia by Alcian blue and toluidine blue and were S100 and collagen-II positive. To our knowledge, this is the first report of the establishment of a human dedifferentiated chondrosarcoma from mutated human embryonic muscle cells, and it is a useful model for the study of the molecular pathogenesis of dedifferentiated CS. IntroductionChondrosarcoma (CS) is the second most frequent primary malignant bone tumor after osteosarcoma and is characterized by basic neoplastic histology with cartilaginous stroma. The most frequent locations are the femur, pelvis and humerus, and 62% of patients are in the fourth, fifth and sixth decades of life (1-4). About 10% of CS undergoes regional anaplastic change, resulting in a high-grade noncartilaginous sarcoma arising within a typically low-grade CS, known as dedifferentiated CS (1-4), this concept was first introduced by Dahlin and Beabout in 1971 (5). They reported 33 cases of well-differentiated CS of bone with additional malignant mesenchymal components, such as fibrosarcoma or osteosarcoma. Some authors prefer instead to use the term CS with additional malignant mesenchymal component because of the morphogenesis of the tumor (5).Dedifferentiated CS is a highly lethal malignancy. Despite adequate, aggressive, initial, wide surgical resection or even amputation, unfortunately, metastases occur early and frequently and commonly involve the lungs, lymph nodes, and viscera (5-12). It is the poorly differentiated component that metastasizes. The prognosis is dismal, with an estimated 5-year survival rate of <10-25% (5-12). Many analyses of dedifferentiated CS are available at the clinico-pathological level, and the cell biology of this neoplasm is still not clearly understood. To our knowledge, there is only one report descr...

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Mutation of p53 with loss of heterozygosity in the osteosarcomatous component of a dedifferentiated chondrosarcoma

Cited by 36 publications

References 19 publications

Establishment of novel human dedifferentiated chondrosarcoma cell line with osteoblastic differentiation

Establishment of novel human dedifferentiated chondrosarcoma cell line with osteoblastic differentiation

Dedifferentiated peripheral chondrosarcoma: a clinicopathologic, immunohistochemical, and molecular analysis of four cases

A novel mutated cell line with characteristics of dedifferentiated chondrosarcoma

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