Frequent occurrence of p53 mutations in rhabdomyosarcoma and leiomyosarcoma, but not in fibrosarcoma and malignant neural tumors.
We have analyzed soft-tissue sarcomas (STS) molecularly for mutations in the tumor-suppressor gene p53 and immunohisto-chemically 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-1 and DO-7) and an mdm2 antibody (IF-2). Out of these, 100 samples were subjected to non-radioactive PCR-SSCP-sequencing analysis. Immunohistochemical detection rate for p53 (range of 57% to 67%) and for mdm2 proteins (range of 19 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.
Würl
P
P
Surgical Clinic, Martin Luther University of Halle-Wittenberg, Halle/S., Germany.
Taubert
H
H
Bache
M
M
Kroll
J
J
Meye
A
A
Berger
D
D
Siermann
A
A
Holzhausen
H J
HJ
Hinze
R
R
Schmidt
H
H
Rath
F W
FW
D001483:Base Sequence; D003062:Codon; D005354:Fibrosarcoma / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007890:Leiomyosarcoma / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009380:Neoplasms, Nerve Tissue / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012208:Rhabdomyosarcoma / Q000235:genetics*
D003062:Codon