Rhei E, Bogomolniy F, Federici M G, Maresco D L, Offit K, Robson M E, Saigo P E, Boyd J
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cancer Res. 1998 Aug 1;58(15):3193-6.
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.
对与BRCA1或BRCA2种系突变相关的遗传性卵巢癌进行了研究，以确定BRCA相关的卵巢肿瘤发生是否需要P53基因的体细胞突变，以及进一步确定这些肿瘤中存在的其他体细胞分子遗传改变谱是否与散发性卵巢癌中已知存在的不同。对40个肿瘤进行了检查，其中29个与BRCA1相关，11个与BRCA2相关，检测P53、K-RAS、ERBB-2、C-MYC和AKT2的突变改变。这些癌症中80%存在P53突变，这表明P53突变很常见，但不是BRCA相关的卵巢肿瘤发生所必需的；值得注意的是，与BRCA1相关癌症中更典型的错义突变谱相比，BRCA2相关癌症中P53突变的缺失或插入比例明显更高。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AKT2的扩增。
