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p53 mutations in chondrosarcoma

R M Terek¹, J H Healey, P Garin-Chesa

¹Department of Orthopaedics, Rhode Island Hospital and Providence Veterans Administration Medical Center, Providence, USA.

Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B

|July 1, 1998

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p53 mutations are rare in chondrosarcoma but occur in high-grade tumors. This study identified a novel p53 point mutation in a dedifferentiated chondrosarcoma, suggesting its role in advanced bone cancer progression.

Area of Science:

Oncology
Molecular Biology
Genetics

Background:

Chondrosarcoma is a primary bone tumor with diverse grades and variants.
The role of p53 gene alterations in chondrosarcoma pathogenesis is not fully understood.

Purpose of the Study:

To investigate p53 overexpression and mutations in chondrosarcoma.
To identify specific p53 mutations and their correlation with tumor grade.

Main Methods:

Evaluated 48 chondrosarcomas using immunohistochemistry (PAb421, PAb1801, PAb240) for p53 expression.
Identified p53 mutations via single-strand conformational polymorphism (SSCP) and DNA sequencing.

Main Results:

Nuclear p53 staining observed in one dedifferentiated chondrosarcoma using PAb421 and PAb1801.

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SSCP analysis revealed abnormalities in the same case, localizing mutations to exons 7 and 8.

DNA sequencing identified a novel G-to-C point mutation at codon 276, resulting in an alanine-to-proline substitution.

Conclusions:

p53 mutations are infrequent in chondrosarcoma but are associated with higher-grade tumors and variants.
The identified point mutation, previously unreported in chondrosarcoma, may contribute to tumor progression.