Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma
Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma
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DOI：
10.1093/jnci/95.6.484
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发表时间：
2003-03-19
期刊：
影响因子：
--
通讯作者：
Shih, IM
中科院分区：
文献类型：
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作者：
Singer, G;Oldt, R;Shih, IM
KRAS及其下游介质之一BRAF的激活突变已在多种人类癌症中被鉴定。为了确定BRAF和KRAS突变在卵巢癌中的作用，我们分析了两种基因的三种常见突变（BRAF的密码子599和KRAS的密码子12和13）。BRAF密码子599或KRAS密码子12和13的突变发生在22例浸润性微乳头状浆液性癌（MPSC;低级别肿瘤）中的15例（68%）和51例浆液性交界性肿瘤（浸润性MPSC的前体病变）中的31例（61%）。没有一个肿瘤同时含有BRAF和KRAS突变。相比之下，分析的72例传统侵袭性高级别浆液性癌均不含BRAF密码子599突变或两种KRAS突变中的任一种。这些BRAF和KRAS突变对低级别浆液性卵巢癌及其前体的明显限制表明，低级别和高级别卵巢浆液性癌通过独立的途径发展。
Activating mutations in KRAS and in one of its downstream mediators, BRAF, have been identified in a variety of human cancers. To determine the role of mutations in BRAF and KRAS in ovarian carcinoma, we analyzed both genes for three common mutations (at codon 599 of BRAF and codons 12 and 13 of KRAS). Mutations in either codon 599 of BRAF or codons 12 and 13 of KRAS occurred in 15 of 22 (68%) invasive micropapillary serous carcinomas (MPSCs; low-grade tumors) and in 31 of 51 (61%) serous borderline tumors (precursor lesions to invasive MPSCs). None of the tumors contained a mutation in both BRAF and KRAS. In contrast, none of the 72 conventional aggressive high-grade serous carcinomas analyzed contained the BRAF codon 599 mutation or either of the two KRAS mutations. The apparent restriction of these BRAF and KRAS mutations to low-grade serous ovarian carcinoma and its precursors suggests that low-grade and high-grade ovarian serous carcinomas develop through independent pathways.