Frequent occurrence of p53 mutations in rhabdomyosarcoma and leiomyosarcoma, but not in fibrosarcoma and malignant neural tumors

✍ Scribed by Peter Würl; Helge Taubert; Matthias Bache; Jens Kroll; Axel Meye; Dieter Berger; Anja Siermann; Hans-Jürgen Holzhausen; Raoul Hinze; Hannelore Schmidt; Friedrich-Wilhelm Rath

• Book ID: 102653626
• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 800 KB
• Volume: 69
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19960822)69:4<317::aid-ijc14>3.0.co;2-2

✦ Synopsis

We have analyzed soft-tissue sarcomas (STS) molecularly for mutations in the tumor-suppressor gene p53 and immunohistochemically for expression of p53 and mdm2 proteins. In this study, tumor samples from 3 groups of soft-tissue sarcomas, i.e., fibrosarcomas, myogenic sarcomas and malignant neural tumors (MNT), were investigated. The methods applied encompass immunohistochemistry on 198 tumor samples using p53 antibodies (DO-I and DO-7) and an mdm2 antibody (IF-2). Out of these, 100 samples were subjected to non-radioactive PCR-SSCP-sequencing analysis. lmmunohistochemical detection rate for p53 (range of 57% to 67%) and for mdm2 proteins (range of I9 to 44%) was similar in all 3 groups. In higher tumor grades, an increased rate of immunopositivity was found for p53 but not for mdm2. Investigation of p53 mutational status revealed 6 mutations in myogenic sarcomas but none in malignant neural tumors or fibrosarcomas, suggesting different roles of p53 in the 3 STS groups. Interestingly, a G + A transition in codon 245 (a CpG site) was found in 3 myogenic sarcomas. Our results and those of others suggest p53 codon 245 as a mutational hotspot in sarcomas, as recognized in carcinomas.