Stability of p53 tumor suppressor gene mutations during the process of metastasis and during chemotherapy.
We analyzed 29 pairs of primary and metastatic lung carcinomas obtained at autopsy for mutations in the p53 gene, using the polymerase chain reaction-single strand conformation polymorphism method (PCR-SSCP). We examined the relationship between p53 gene mutations and the development of metastasis, and the stability of p53 gene mutations during chemotherapy. The tumors consisted of six small cell carcinomas, 13 adenocarcinomas, eight squamous cell carcinomas, one large cell carcinoma, and one adeno-squamous cell carcinoma. PCR-SSCP analysis showed that three small cell carcinomas (50%), three adenocarcinomas (23%), two squamous cell carcinomas (25%), and one large cell carcinoma (100%) had p53 gene mutations. All these abnormalities were found between exon five and exon eight. The mutations in the primary tumors and the metastatic tumors were identical. These results suggest that p53 gene mutations occur before distant metastases develop, and that they may be stable during the process of metastasis. There were nine metastatic tumor samples that existed before the patients received chemotherapy. These samples showed identical p53 mutations as the corresponding primary tumor. This suggests that anticancer drugs rarely induce p53 gene mutations.
Taniguchi
Y
Y
Fourth Department of Internal Medicine, Nippon Medical School Main Hospital, Tokyo, Japan.
Gemma
A
A
Takeda
Y
Y
Takenaka
K
K
Niitani
H
H
Kudoh
S
S
Shimada
T
T
D001483:Base Sequence; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary*; D008297:Male; D009154:Mutation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
D004273:DNA, Neoplasm