P53 GENE-MUTATIONS IN OSTEOSARCOMAS OF LOW-GRADE MALIGNANCY

Alterations in tumor suppressor gene p53, localized on chromosome 17p1 3, are considered to play a significant role in the initiation and, to some extent, even in the progression of various malignant tumors. In this respect, investigations on conventional highly malignant osteosar comas have shown a mutation rate of approximately 20%. However, curren tly data on the mutation rate in the group of variant histology osteos arcomas of low-grade malignancy do not exist. Therefore, we investigat ed a panel of low malignant entities (five low malignant intramedullar y osteosarcomas grade 1; one intramedullary osteosarcoma grade 2; eigh t parosteal osteosarcomas, including one local recurrence grades 1 and 2, and five periosteal osteosarcomas grade 2) with polymerase chain r eaction/single-strand conformation polymorphism (PCR-SSCP) analysis fo cusing on exons 4 to 8 of the p53 gene followed by direct sequencing. Point mutations were found in one low-grade osteoblastoma-like osteosa rcoma and in two periosteal osteosarcomas grade 2 (one missense, one s ilent, and one nonsense mutation). This mutation rate of 15.7% (3 of 1 9) is comparable to that determined in highly malignant osteosarcomas. Moreover, the analysis of clinical data did not show any difference i n the behavior of tumors with p53 mutations compared with those withou t. Therefore, we suggest that alterations in p53 gene are an early eve nt in the tumorigenesis of malignant osteoblastic tumors without impac t on progression of these tumors, Copyright (C) 1998 by W.B. Saunders Company.