Molecular genetic characterization of BRCA1- and BRCA2-linked hereditary ovarian cancers.
Molecular genetic characterization of BRCA1- and BRCA2-linked hereditary ovarian cancers.
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发表时间：
1998-08
期刊：
影响因子：
11.2
通讯作者：
E. Rhei;F. Bogomolniy;M. Federici;D. Maresco;K. Offit;M. Robson;P. Saigo;J. Boyd
中科院分区：
文献类型：
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作者：
E. Rhei;F. Bogomolniy;M. Federici;D. Maresco;K. Offit;M. Robson;P. Saigo;J. Boyd
研究与BRCA 1或BRCA 2生殖系突变相关的遗传性卵巢癌，以确定BRCA连锁的卵巢肿瘤发生是否需要P53基因的体细胞突变，以及这些肿瘤中存在的其他体细胞分子遗传学改变谱是否与散发性卵巢癌中已知的不同。对40个肿瘤（29个与BRCA 1相关，11个与BRCA 2相关）进行了P53、K-RAS、ERBB-2、C-MYC和AKT 2突变改变检查。这些癌症中80%存在P53突变，表明P53突变是常见的，但不是BRCA相关卵巢肿瘤发生所必需的;值得注意的是，与BRCA 1相关癌症中更典型的错义突变谱相比，BRCA 2相关癌症中P53突变的缺失或插入比例显着更高。此外，BRCA相关的卵巢癌似乎通过一种独特的肿瘤发生途径发展，该途径不涉及K-RAS突变或ERBB-2、C-MYC或AKT 2扩增。
Hereditary ovarian cancers associated with germline mutations in either BRCA1 or BRCA2 were studied to determine whether somatic mutation of the P53 gene is required for BRCA-linked ovarian tumorigenesis and further, whether the spectrum of additional somatic molecular genetic alterations present in these tumors differs from that known to exist in sporadic ovarian cancers. Forty tumors, 29 linked to BRCA1 and 11 linked to BRCA2, were examined for mutational alterations in P53, K-RAS, ERBB-2, C-MYC, and AKT2. The presence of a P53 mutation in 80% of these cancers indicates that P53 mutation is common but not required for BRCA-linked ovarian tumorigenesis; notably, a significantly higher proportion of the P53 mutations in BRCA2-linked cancers were deletions or insertions compared with the more typical spectrum of missense mutations seen in BRCA1-linked cancers. Additionally, BRCA-linked ovarian carcinomas seem to develop through a unique pathway of tumorigenesis that does not involve mutation of K-RAS or amplification of ERBB-2, C-MYC, or AKT2.