A novel somatic MAPK1 mutation in primary ovarian mixed germ cell tumors
A novel somatic MAPK1 mutation in primary ovarian mixed germ cell tumors
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原发性卵巢混合生殖细胞肿瘤中一种新的体细胞 MAPK1 突变
DOI：
10.3892/or.2015.4402
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发表时间：
2016-02-01
期刊：
影响因子：
4.2
通讯作者：
Huang, Ou-Ping
中科院分区：
文献类型：
--
作者：
Zou, Yang;Deng, Wei;Huang, Ou-Ping
最近的一项外显子组测序研究显示，宫颈癌中普遍存在丝裂原活化蛋白激酶1 (MAPK1) p.E322K突变。卵巢癌是否也有MAPK1突变，这在很大程度上仍然是未知的。由于旁系基因突变在人类恶性肿瘤中经常共同发生，我们在这里通过DNA测序分析了263例卵巢癌中MAPK1和旁系MAPK3突变的存在。在18例卵巢混合生殖细胞肿瘤中，有2例（11.1%）发现了先前未报道的MAPK1 p.D321N体细胞突变，而在我们的样本中未检测到其他MAPK1或MAPK3突变。值得注意的是，受双侧卵巢癌影响的MAPK1突变样本OCC-115在右侧卵巢中携带MAPK1突变，而左侧卵巢保持完整，这意味着卵巢混合生殖细胞瘤的遗传改变可能是不同的，即使在遗传背景和肿瘤微环境相似的患者中也是如此。进化保守和蛋白结构建模分析结果提示MAPK1 p.D321N突变可能具有致病性。此外，蛋白磷酸酶2调控亚基a （PPP2R1A）、环指蛋白43 （RNF43）、DNA定向聚合酶epsilon （POLE1）、核糖核酸酶III型（DICER1）、ccctc结合因子（CTCF）、核糖体蛋白L22 （RPL22）、DNA甲基转移酶3 α (DNMT3A)、转化/转录结构域相关蛋白（TRRAP）、异柠檬酸脱氢酶（IDH）1和IDH2在卵巢混合生殖细胞肿瘤中未检测到突变。暗示这些基因改变可能与恶性肿瘤发展中的MAPK1突变无关。本研究首次在卵巢混合生殖细胞肿瘤中发现了一种以前未报道的MAPK1突变，该突变可能积极参与了该疾病的肿瘤发生。
A recent exome-sequencing study revealed prevalent mitogen-activated protein kinase 1 (MAPK1) p.E322K mutation in cervical carcinoma. It remains largely unknown whether ovarian carcinomas also harbor MAPK1 mutations. As paralogous gene mutations co-occur frequently in human malignancies, we analyzed here a total of 263 ovarian carcinomas for the presence of MAPK1 and paralogous MAPK3 mutations by DNA sequencing. A previously unreported MAPK1 p.D321N somatic mutation was identified in 2 out of 18 (11.1%) ovarian mixed germ cell tumors, while no other MAPK1 or MAPK3 mutation was detected in our samples. Of note, OCC-115, the MAPK1-mutated sample with bilateral cancerous ovaries affected, harbored MAPK1 mutation in the right ovary while retained the left ovary intact, implicating that the genetic alterations underlying ovarian mixed germ cell tumor may be different, even in patients with similar genetic backgrounds and tumor microenvironments. The results of evolutionary conservation and protein structure modeling analysis implicated that MAPK1 p.D321N mutation may be pathogenic. Additionally, mutations in protein phosphatase 2 regulatory subunit a (PPP2R1A), ring finger protein 43 (RNF43), DNA directed polymerase epsilon (POLE1), ribonuclease type III (DICER1), CCCTC-binding factor (CTCF), ribosomal protein L22 (RPL22), DNA methyltransferase 3 alpha (DNMT3A), transformation/transcription domain-associated protein (TRRAP), isocitrate dehydrogenase (IDH)1 and IDH2 were not detected in ovarian mixed germ cell tumors, implicating these genetic alterations may be not associated with MAPK1 mutation in the development of this malignancy. The present study identified a previously unreported MAPK1 mutation in ovarian mixed germ cell tumors for the first time, and this mutation may be actively involved in the tumorigenesis of this disease.