Comparison of p53 mutations in patients with localized osteosarcoma and metastatic osteosarcoma.
BACKGROUND
In some malignancies, p53 mutations are associated with tumor progression. To address the role of p53 mutations in the development and progression of osteosarcoma, the authors analyzed specimens from 247 patients with primary localized osteosarcomas and 25 patients with osteosarcomas that were metastatic at the time of diagnosis. The group included 27 matched biopsy-resection specimens and 21 biopsy-metastasis paired specimens.


METHODS
The authors examined the nature and location of p53 mutations (exons 4-10) by polymerase chain reaction-single-strand conformation polymorphism and confirmed mutations by direct DNA sequencing.


RESULTS
The overall frequency of p53 mutations was 22% (60 of 272 specimens), with 13 of 60 mutations located in exons 4 or 10. A similar proportion of localized osteosarcomas had alterations of the p53 gene (55 of 247 specimens; 22.3%) compared with tumors from patients who had metastases at the time of diagnosis (5 of 25 specimens; 20%; P = 0.96). Patients who had p53 missense mutations were older compared with patients who had nonsense alterations or a wild type gene (P = 0.01). Examination of paired biopsy-resection and biopsy-metastasis specimens revealed that the p53 status was concordant between the biopsy and later tumor specimens in all patients.


CONCLUSIONS
The p53 mutation status did not differentiate between patients who presented with a localized osteosarcoma and those who presented with metastases at the time of diagnosis. The current data indicate that p53 mutations are not late events in osteosarcoma tumor progression, because they are evident before the development of metastases. The inclusion of exons 4 and 10 increased the sensitivity of the analysis.
Gokgoz
N
N
Fred A. Litwin Center for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Wunder
J S
JS
Mousses
S
S
Eskandarian
S
S
Bell
R S
RS
Andrulis
I L
IL
D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology*; D002648:Child; D005260:Female; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation; D012516:Osteosarcoma / Q000235:genetics* / Q000556:secondary*; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis