Frequent somatic mutations of the telomerase reverse transcriptase promoter in ovarian clear cell carcinoma but not in other major types of gynaecological malignancy.
Frequent somatic mutations of the telomerase reverse transcriptase promoter in ovarian clear cell carcinoma but not in other major types of gynaecological malignancy.
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DOI：
10.1002/path.4315
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发表时间：
2014-03
影响因子：
7.3
通讯作者：
Wang, Tian-Li
中科院分区：
文献类型：
--
作者：
Wu, Ren-Chin;Ayhan, Ayse;Maeda, Daichi;Kim, Kyu-Rae;Clarke, Blaise A.;Shaw, Patricia;Chui, Michael Herman;Rosen, Barry;Shih, Ie-Ming;Wang, Tian-Li
端粒酶逆转录酶（telomerase reverse transcriptase，TERT）的上调表达和端粒长度的维持在肿瘤的发生发展中起重要作用。最近的研究表明，体细胞功能获得性突变在TERT启动子作为一种机制，促进转录激活的TERT，但是，目前还不清楚这种遗传异常是否普遍存在于妇科肿瘤。我们在总共525例妇科癌症中进行了突变分析，并将TERT启动子突变与临床病理特征相关联。除卵巢透明细胞癌（233例中有37例（15.9%）发现突变）外，大多数妇科恶性肿瘤均为野生型。TERT启动子突变似乎不是肿瘤发生的早期事件，因为在与卵巢透明细胞癌相关的相邻子宫内膜异位症中未检测到。卵巢透明细胞癌细胞株与TERT启动子突变表现出较高的TERTmRNA表达比野生型序列（p = 0.0238）。在卵巢透明细胞癌中，TERT启动子突变倾向于与ARID1A蛋白表达缺失（p= 4.4×10−9）和PIK3CA突变（p= 0.0019）相互排斥。未观察到卵巢透明细胞癌与疾病特异性生存率相关。上述结果，结合我们以前的报告显示，较长的端粒在卵巢透明细胞癌相对于其他类型的卵巢癌，提示端粒生物学畸变可能在卵巢透明细胞癌的发病机制中发挥重要作用。
Up-regulated expression of telomerase reverse transcriptase (TERT) and subsequent maintenance of telomere length are essential in tumor development. Recent studies have implicated somatic gain-of-function mutations at the TERT promoter as one of the mechanisms that promote transcriptional activation of TERT; however, it remains unclear whether this genetic abnormality is prevalent in gynecologic neoplasms. We performed mutational analysis in a total of 525 gynecological cancers, and correlated TERT promoter mutations with clinicopathological features. With the exception of ovarian clear cell carcinomas, in which mutations were found in 37 (15.9%) of 233 cases, the majority of gynecologic malignancies were wild-type. TERT promoter mutation does not appear to be an early event during oncogenesis, as it was not detected in the contiguous endometriosis associated with ovarian clear cell carcinoma. Ovarian clear cell carcinoma cell lines with TERT promoter mutations exhibited higher TERT mRNA expression than those with wild-type sequences (p = 0.0238). TERT promoter mutation tended to be mutually exclusive with loss of ARID1A protein expression (p= 4.4×10−9) and PIK3CA mutation (p= 0.0019) in ovarian clear cell carcinomas. No associations with disease-specific survival were observed for ovarian clear cell carcinoma. The above results, in conjunction with our previous report showing longer telomeres in ovarian clear cell carcinomas relative to other types of ovarian cancer, suggests that aberrations in telomere biology may play an important role in the pathogenesis of ovarian clear cell carcinoma.
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DOI：
10.1126/science.1170633
发表时间：
2009-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
de Lange T
通讯作者：
de Lange T
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16
作者：
Lin, Yuanji;Yang, Ying;Li, Weihua;Chen, Qi;Li, Jie;Pan, Xiao;Zhou, Lina;Liu, Changwei;Chen, Chunsong;He, Jianqin;Cao, Hongcui;Yao, Hangping;Zheng, Li;Xu, Xiaowei;Xia, Zongping;Ren, Jiangtao;Xiao, Lei;Li, Lanjuan;Shen, Binghui;Zhou, Honglin;Wang, Ying-Jie
通讯作者：
Wang, Ying-Jie
影响因子：
3.6
作者：
Li, Hongxia;Gao, Quanli;Lu, Shih Hsin
通讯作者：
Lu, Shih Hsin
DOI：
10.1038/modpathol.2011.67
发表时间：
2011-08
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
--
作者：
Kuhn E;Meeker AK;Visvanathan K;Gross AL;Wang TL;Kurman RJ;Shih IeM
通讯作者：
Shih IeM