Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma
Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma
复制标题
中国卵巢子宫内膜样癌患者中常见 POLE1 p.S297F 突变
DOI：
10.1016/j.mrfmmm.2014.01.003
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发表时间：
2014-03-01
影响因子：
2.3
通讯作者：
He, Ming
中科院分区：
文献类型：
--
作者：
Zou, Yang;Liu, Fa-Ying;He, Ming
DNA聚合酶催化亚基（POLE 1）主要在核DNA复制和修复中发挥作用。近年来，POLE 1基因突变在结直肠癌和子宫内膜癌中检出率较高，而在其他几种肿瘤中检出率较低，其中p.P286R和p.V411L突变是人类肿瘤中潜在的突变热点。然而，POLE 1在卵巢癌中的突变频率在很大程度上仍然未知。在此，我们通过直接测序筛选了251例不同亚型的卵巢癌患者的POLE 1热点突变。在37例卵巢类卵巢癌患者中有3例（8.1%）发现了杂合子体细胞POLE 1突变p.S297F（c.890C>T），而不是在其他癌症类型中观察到的p.P286R和p.V411L热点突变;该突变在进化上从智人到裂殖酵母高度保守。值得注意的是，POLE 1突变与卵巢癌相关PPP 2 R1 A（蛋白磷酸酶2，调节亚基A，α）基因突变共存于一名46岁的患者中，该患者也被诊断为良性卵巢异位子宫内膜异位症。此外，一名45岁POLE 1突变的卵巢类肉瘤患者也被诊断为子宫平滑肌瘤，而另一名52岁POLE 1突变的患者没有表现出其他独特的临床表现。与卵巢上皮样癌中POLE 1突变的高频率相反，在其他亚型卵巢癌患者中未发现POLE 1突变。我们的研究结果首次表明，POLE 1 p.S297F突变，而不是p.P286R和p.V411L热点突变在其他类型的卵巢癌中观察到，是中国人卵巢上皮样癌中常见的，但在其他亚型卵巢癌中不存在。这些结果提示POLE 1 p.S297F突变可能与卵巢上皮样癌的发生有关，而与其他类型的卵巢上皮样癌的发生无关。(C)2014爱思唯尔有限公司版权所有。
The catalytic subunit of DNA polymerase epsilon (POLE1) functions primarily in nuclear DNA replication and repair. Recently, POLE1 mutations were detected frequently in colorectal and endometrial carcinomas while with lower frequency in several other types of cancer, and the p.P286R and p.V411L mutations were the potential mutation hotspots in human cancers. Nevertheless, the mutation frequency of POLE1 in ovarian cancer still remains largely unknown. Here, we screened a total of 251 Chinese samples with distinct subtypes of ovarian carcinoma for the presence of POLE1 hotspot mutations by direct sequencing. A heterozygous somatic POLE1 mutation, p.S297F (c.890C>T), but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was identified in 3 out of 37 (8.1%) patients with ovarian endometrioid carcinoma; this mutation was evolutionarily highly conserved from Homo sapiens to Schizosaccharomyces. Of note, the POLE1 mutation coexisted with mutation in the ovarian cancer-associated PPP2R1A (protein phosphatase 2, regulatory subunit A, alpha) gene in a 46-year-old patient, who was also diagnosed with ectopic endometriosis in the benign ovary. In addition, a 45-year-old POLE1-mutated ovarian endometrioid carcinoma patient was also diagnosed with uterine leiomyoma while the remaining 52-year-old POLE1-mutated patient showed no additional distinctive clinical manifestation. In contrast to high frequency of POLE1 mutations in ovarian endometrioid carcinoma, no POLE1 mutations were identified in patients with other subtypes of ovarian carcinoma. Our results showed for the first time that the POLE1 p.S297F mutation, but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was frequent in Chinese ovarian endometrioid carcinoma, but absent in other subtypes of ovarian carcinoma. These results implicated that POLE1 p.S297F mutation might be actively involved in the pathogenesis of ovarian endometrioid carcinoma, but might not be actively involved in other subtypes of ovarian carcinoma. (C) 2014 Elsevier B.V. All rights reserved.