PPP2R1A mutations are common in the serous type of endometrial cancer
PPP2R1A mutations are common in the serous type of endometrial cancer
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DOI：
10.1002/mc.20850
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发表时间：
2012-10-01
影响因子：
4.6
通讯作者：
Risinger, John I.
中科院分区：
文献类型：
--
作者：
Nagendra, Deepak C.;Burke, James, III;Risinger, John I.
最近，无偏测序工作确定了透明细胞卵巢癌（OCC）中的PPP 2 R1 A突变。在子宫浆液性癌中也发现了高频率的类似突变。由于子宫内膜是从相同的发育前体发育而来，我们进一步研究了PPP 2 R1 A突变也可能发生在不同组织学亚型的子宫癌中的假设。我们在22个子宫癌细胞系模型和10个原发性癌症中对PPP 2 R1 A进行了测序。我们发现没有突变的细胞系最初来源于类胡萝卜素（n？=？未分化组（n = 13）;透明细胞（n = 3）;癌肉瘤（n = 1）; 3)癌的然而，我们在ACI-158浆液性癌细胞系中发现了CCC（Pro）到CGC（Arg）密码子179的突变，在原发性浆液性癌中发现了CCC（Pro）到CTC（Leu）的突变，以及在低分化类胶质瘤中发现了CGC（Arg）到CAC（His）密码子258的突变。我们对一组子宫内膜恶性肿瘤进行了测序（n =？181)发现了12个变种人重要的是，我们证实了25例浆液性癌中8例（32%）的高频率突变，这是一种公认的预后不良的亚型。突变在类胶质瘤中不常见，在透明细胞和癌肉瘤亚型中不存在。PPP 2 R1 A突变区在物种之间是保守的，并且已知与PP 2A酶的调节亚基相互作用。PPP 2 R1 A突变型子宫内膜癌可能是个性化药物治疗的良好候选者，特别是对于患有子宫癌的致命浆液性组织学变异的女性。(c)2011 Wiley Periodicals，Inc.
Recently unbiased sequencing efforts identified PPP2R1A mutations in clear cell ovarian cancers (OCC). Similar mutations were also noted with high frequency in uterine serous carcinoma. Because the endometrium develops from the same developmental precursors we further examined the hypothesis that PPP2R1A mutations might also occur in diverse histologic subtypes of uterine cancer. We sequenced the PPP2R1A in 22 cell line models of uterine cancer and 10 primary cancers. We found no mutations in the cell lines originally derived from endometrioid (n?=?13), undifferentiated (n?=?3), clear cell (n?=?1), and carcinosarcoma (n?=?3) cancers. However, we found a CCC (Pro) to CGC (Arg) codon 179 mutation in the ACI-158 serous carcinoma cell line, a CCC (Pro) to CTC (Leu) in a primary serous carcinoma as well as a CGC (Arg) to CAC (His) codon 258 mutation in a poorly differentiated endometrioid cancer. We sequenced a large panel of endometrial malignancies (n?=?181) and found 12 mutants. Importantly, we confirmed a high frequency of mutation in 8 of 25 (32%) serous carcinomas a subtype with well-recognized poor prognosis. Mutations were infrequent in endometrioid cancer and absent in clear cell and carcinosarcoma subtypes. The PPP2R1A mutation regions are conserved among species and known to interact with the regulatory subunits of the PP2A enzyme. PPP2R1A mutant endometrial cancers may represent good candidates for personalized drug therapies particularly for women with the lethal serous histologic variant of uterine cancer. (c) 2011 Wiley Periodicals, Inc.