Role of KRAS and BRAF gene mutations in mucinous ovarian carcinoma
Role of KRAS and BRAF gene mutations in mucinous ovarian carcinoma
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DOI：
10.1016/s0090-8258(03)00264-6
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发表时间：
2003-08-01
影响因子：
4.7
通讯作者：
Boyd, J
中科院分区：
文献类型：
--
作者：
Gemignani, ML;Schlaerth, AC;Boyd, J
目标.本研究的目的是对各种组织学亚型的浸润性上皮性卵巢癌中KRAS癌基因突变的患病率进行全面评估，并对发现KRAS突变常见的任何亚组进行评估，以解决以下假设：无KRAS突变的肿瘤通过BRAF癌基因突变持续交替激活该信号通路。方法.根据组织学分类，从该机构10年期间共选择了104例原发性浸润性上皮性卵巢癌进行研究。组织学类型：浆液性21例，类浆液性30例，透明细胞31例，粘液性22例。从患者记录中提取其他临床和病理学信息，并对所有病例进行病理学审查。使用从所有肿瘤标本中分离的DNA对KRAS基因外显子2（包含密码子12）进行直接序列分析。对22例卵巢粘液性癌组织进行BRAF基因外显子II和15的序列分析。结果激活性KRAS突变在粘液性肿瘤中（50%）比在所有其他组织学类型中（5%; P < 10（-7））更常见。KRAS突变在I期肿瘤中比在晚期肿瘤中更常见（P = 0.0004）。在具有KRAS突变的II型粘液性肿瘤中，6例为苗勒管（宫颈内）型，5例为胃肠道型。没有发现粘液性肿瘤携带BRAF突变。结论.这些数据表明，KRAS癌基因突变存在于几种组织学类型的浸润性上皮性卵巢癌，特别是I期肿瘤，但常见于粘液组织学肿瘤。突变在苗勒管和胃肠道类型的粘液性卵巢癌中同样普遍。与经常受KRAS突变影响的其他实体瘤类型相反，没有KRAS突变的粘液性卵巢癌没有通过BRAF癌基因突变持续该信号传导途径的替代激活。(C)2003 Elsevier Science（美国）。All rights reserved.
Objectives. The goals of this study were to perform a comprehensive assessment of the prevalence of KRAS oncogene mutations in invasive epithelial ovarian carcinomas of various histologic subtypes, and for any subgroup(s) in which KRAS mutation was found to be common, to address the hypothesis that those tumors without KRAS mutation had sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene. Methods. A total of 104 primary, invasive epithelial ovarian carcinomas from a 10-year period at this institution were selected for study based on histologic classification. The histologic cell type was serous in 21 cases, endometrioid in 30 cases, clear cell in 31 cases, and mucinous in 22 cases. Additional clinical and pathological information was abstracted from patient records, and pathology review was performed for all cases. Direct sequence analysis of exon 2 of the KRAS gene, containing codon 12, was performed using DNA isolated from all tumor specimens. Sequence analyses of exons I I and 15 of the BRAF gene were performed for the 22 cases of mucinous ovarian carcinoma. Results. Activating KRAS mutations were more common in mucinous tumors (50%) than in all other histologic types combined (5%; P < 10(-7)). Mutation of KRAS was more common in stage I tumors than in advanced stage tumors (P = 0.0004). Of the I I mucinous tumors with KRAS mutations, 6 were of Mullerian (endocervical) type and 5 were of gastrointestinal type. No mucinous tumor was found to harbor a BRAF mutation. Conclusions. These data indicate that KRAS oncogene mutations exist in several histologic types of invasive epithelial ovarian carcinoma, especially stage I tumors, but are common only in tumors of mucinous histology. Mutations are equally prevalent in mucinous ovarian cancers of Mullerian and gastrointestinal types. In contrast to other solid tumor types frequently affected by KRAS mutation, mucinous ovarian cancers without a KRAS mutation have not sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene. (C) 2003 Elsevier Science (USA). All rights reserved.