Alterations of the p53 tumor suppressor gene and its association with activation of the c-K-ras-2 protooncogene in premalignant and malignant lesions of the human uterine endometrium

摘要: We previously reported (T. Enomoto et al. , Cancer Res., 50: 6139–6145, 1990; T. 51: 5308–5314, 1991) a significant frequency of activating point mutations in codon 12 the c-K- ras -2 protooncogene endometrial adenocarcinoma and its premalignant precursor lesions (series 1 2). To reveal role p53 tumor suppressor gene development to study association alterations with K- activation, an additional 28 adenocarcinomas 11 atypical uterine hyperplasias 3), as well cases (10 having or N- activation) 2 hyperplasia from series 2, were screened for presence alterations. Allelic loss, recognized at polymorphic site 72 gene, was detected 6 19 (32%) informative 4 (25%) by restriction fragment length polymorphism analysis single-strand conformation polymerase chain reaction (PCR)-amplified DNA fragments. Mutations highly conserved regions PCR-amplified found 9 40 (23%) 13 (8%) that studied. significantly more frequently clinical grade 3 (G3) cancers (6 14, 43%) than G1-G2 (3 26, 12%) ( P = 0.033). subsequently confirmed direct sequencing. Single missense base substitutions carcinoma one case hyperplasia. Deletions single bases each carcinoma, insertion third case. Point also identified tumors sequencing fragments exons 2. codons 7 3, but none exon (codons 59–63). The spectrum almost identical what we suggesting possible mutagen might be responsible both . However, there no correlation between activation these tumors. It appears inactivation plays adenocarcinoma. In contrast which commonly occurs early event, usually later event carcinogenesis, independently activation.