BRCA1/2 mutation status influences somatic genetic progression in inherited and sporadic epithelial ovarian cancer cases.
BRCA1/2 mutation status influences somatic genetic progression in inherited and sporadic epithelial ovarian cancer cases.
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发表时间：
2003-01
期刊：
影响因子：
11.2
通讯作者：
S. Ramus;P. Pharoah;P. Harrington;C. Pye;B. Werness;L. Bobrow;A. Ayhan;D. Wells;A. Fishman;M. Gore;R. Dicioccio;M. Piver;A. Whittemore;B. Ponder;S. Gayther
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作者：
S. Ramus;P. Pharoah;P. Harrington;C. Pye;B. Werness;L. Bobrow;A. Ayhan;D. Wells;A. Fishman;M. Gore;R. Dicioccio;M. Piver;A. Whittemore;B. Ponder;S. Gayther
中期比较基因组杂交分析了141例上皮性卵巢癌的遗传变异谱，这些上皮性卵巢癌来自BRCA 1和BRCA 2突变携带者、家族性非BRCA 1/2上皮性卵巢癌个体和非家族性上皮性卵巢癌女性。在几乎所有的肿瘤中发现了多种遗传改变。一些改变的高频率表明在卵巢肿瘤发展过程中通常改变的基因的位置。在多个染色体区域中，四种肿瘤类型之间的改变频率存在显著差异，表明BRCA 1/2突变状态和卵巢癌家族史影响卵巢癌进展的体细胞遗传途径。这些发现得到了分层聚类分析的支持，该分析确定了在肿瘤发生过程中倾向于一起发生的遗传事件和特定类型肿瘤特有的几种改变。此外，一些遗传改变与肿瘤分化和疾病阶段的差异密切相关。综上所述，这些数据提供了分子遗传学证据，支持以前的组织病理学研究结果，这表明卵巢和乳腺肿瘤的临床特征在BRCA 1/2突变状态和/或癌症家族史方面存在差异。
Metaphase comparative genomic hybridization was used to analyze the spectrum of genetic alterations in 141 epithelial ovarian cancers from BRCA1 and BRCA2 mutation carriers, individuals with familial non-BRCA1/2 epithelial ovarian cancer, and women with nonfamilial epithelial ovarian cancer. Multiple genetic alterations were identified in almost all tumors. The high frequency with which some alterations were identified suggests the location of genes that are commonly altered during ovarian tumor development. In multiple chromosome regions, there were significant differences in alteration frequency between the four tumor types suggesting that BRCA1/2 mutation status and a family history of ovarian cancer influences the somatic genetic pathway of ovarian cancer progression. These findings were supported by hierarchical cluster analysis, which identified genetic events that tend to occur together during tumorigenesis and several alterations that were specific to tumors of a particular type. In addition, some genetic alterations were strongly associated with differences in tumor differentiation and disease stage. Taken together, these data provide molecular genetic evidence to support previous findings from histopathological studies, which suggest that clinical features of ovarian and breast tumors differ with respect to BRCA1/2 mutation status and/or cancer family history.