Whole exome sequence analysis of serous borderline tumors of the ovary.
Whole exome sequence analysis of serous borderline tumors of the ovary.
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DOI：
10.1016/j.ygyno.2013.06.007
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发表时间：
2013-09
影响因子：
4.7
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Boyd J;Luo B;Peri S;Wirchansky B;Hughes L;Forsythe C;Wu H
浆液性交界性肿瘤（SBT）是一种独特的组织病理学实体的卵巢，被认为是介于良性囊腺瘤和浸润性低级别浆液性癌。虽然KRAS或BRAF基因的体细胞突变，以及很少的ERBB2基因，在SBT中已得到很好的表征，但尚未描述其他遗传改变。为了更全面地了解SBT的分子遗传结构，我们对这种肿瘤类型进行了全外显子组测序。在病理检查和激光捕获显微切割以富集肿瘤细胞之后，从两个独立的SBT的DNA制备全外显子组，并进行大规模平行DNA测序。这两种肿瘤都含有BRAF基因的激活突变。总共确定了15个额外的体细胞突变，其中9个在一个肿瘤中，6个在另一个肿瘤中。11个是错义突变，4个是无义突变或缺失突变。在这项研究中发现的16个基因中，有14个基因在其他癌症中也发生了突变。此外，这些基因中有12个在卵巢癌中发生突变。FBXW7和KIAA1462基因是值得注意的候选者，在浆液性边界肿瘤发生中具有致病作用。这些发现表明，极少数的体细胞基因突变是卵巢SBT的特征，从而支持其分类为相对遗传稳定的肿瘤类型。本文所述的突变基因代表了卵巢SBT发病机制的新候选基因。
Serous borderline tumor (SBT) is a unique histopathologic entity of the ovary, believed to be intermediate between benign cystadenoma and invasive low-grade serous carcinoma. While somatic mutations in the KRAS or BRAF, and rarely ERBB2, genes have been well characterized in SBTs, other genetic alterations have not been described. Toward a more comprehensive understanding of the molecular genetic architecture of SBTs, we undertook whole exome sequencing of this tumor type. Following pathologic review and laser capture microdissection to enrich for tumor cells, whole exomes were prepared from DNA of two independent SBTs and subjected to massively parallel DNA sequencing. Both tumors contained an activating mutation of the BRAF gene. A total of 15 additional somatic mutations were identified, nine in one tumor and six in the other. Eleven were missense mutations and four were nonsense or deletion mutations. Fourteen of the 16 genes found to be mutated in this study have been reported to be mutated in other cancers. Furthermore, 12 of these genes are mutated in ovarian cancers. The FBXW7 and KIAA1462 genes are noteworthy candidates for a pathogenic role in serous borderline tumorigenesis. These findings suggest that a very small number of somatic genetic mutations are characteristic of SBTs of the ovary, thus supporting their classification as a relatively genetically stable tumor type. The mutant genes described herein represent novel candidates for the pathogenesis of ovarian SBT.
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DOI：
10.1097/pas.0b013e3181cf3d79
发表时间：
2010-03
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Kurman RJ;Shih IeM
通讯作者：
Shih IeM
影响因子：
7.3
作者：
Ahmed, Ashour Ahmed;Etemadmoghadam, Dariush;Temple, Jillian;Lynch, Andy G.;Riad, Mohamed;Sharma, Raghwa;Stewart, Colin;Fereday, Sian;Caldas, Carlos;DeFazio, Anna;Bowtell, David;Brenton, James D.
通讯作者：
Brenton, James D.
影响因子：
11.2
作者：
Kuo KT;Guan B;Feng Y;Mao TL;Chen X;Jinawath N;Wang Y;Kurman RJ;Shih IeM;Wang TL
通讯作者：
Wang TL
影响因子：
3.3
作者：
Seidman, JD;Soslow, RA;Copeland, LJ
通讯作者：
Copeland, LJ
DOI：
10.1111/j.1525-1438.2006.00853.x
发表时间：
2007-07-01
影响因子：
4.8
作者：
Ueda, M.;Toji, E.;Noda, S.
通讯作者：
Noda, S.