Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, 350-1241 Saitama, Japan.
Department of Obstetrics and Gynecology, Juntendo University, Bunkyo-ku, 113-8431 Tokyo, Japan.
Endocr J. 2020 Feb 28;67(2):219-229. doi: 10.1507/endocrj.EJ19-0283. Epub 2019 Nov 19.
Ovarian cancer has the highest mortality rate among gynecological cancers. Gene mutations are involved in the carcinogenesis, metastasis, and therapeutic response in ovarian cancer. However, the variety and proportion of gene mutation is not fully analyzed in Japanese ovarian cancer patients, especially, in those with recurrent tumors. In the present study, RNA-sequencing was performed for 32 clinical ovarian specimens obtained from 24 Japanese patients (24 primary cancer specimens and 8 recurrent specimens paired with corresponding primary cancer specimens). Mutations in 24 primary specimens were analyzed by comparing the sequence data mapped on RefSeq genes with those in the public online databases BRCA Exchange, COSMIC, ClinVar, and cBioportal. Mutations were observed in TP53 in 16 specimens (67%), BRCA1 in 9 (38%), BRCA2 in 13 (54%), ARID1A in 3 (13%), PIK3CA in 2 (8%), KRAS in 1 (4%), PTEN in 1 (4%), and CTNNB1 in 1 (4%), excluding synonymous mutations. Among those identified muations, 13 of 14 mutations in TP53, 10 of 11 mutations of BRCA1, 10 of 23 mutation positions of BRCA2, none of 7 mutations of ARID1A, 1 mutation of PIK3CA, and 1 mutation of CTNNB1 were consistent with those reported in the public online databases; however, the other mutations identified were novel. Comparison between matched-paired specimens of primary and recurrent tumors revealed the changes of mutational status in expressed RNAs. RNA-sequencing-based mutation analysis will be useful to reveal ethnic differences of gene mutations in ovarian cancer and to understand the contribution of gene mutations to recurrence.
卵巢癌是妇科癌症中死亡率最高的癌症。基因突变参与了卵巢癌的发生、转移和治疗反应。然而，在日本卵巢癌患者中，特别是在复发性肿瘤患者中，基因突变的种类和比例尚未得到充分分析。在本研究中，对 24 名日本患者（24 名原发性癌症标本和 8 名与相应原发性癌症标本配对的复发性标本）的 32 个临床卵巢标本进行了 RNA 测序。通过将映射到 RefSeq 基因的序列数据与 BRCA Exchange、COSMIC、ClinVar 和 cBioportal 等公共在线数据库进行比较，分析了 24 个原发性标本中的突变。在 16 个标本（67%）中观察到 TP53 突变，在 9 个标本（38%）中观察到 BRCA1 突变，在 13 个标本（54%）中观察到 BRCA2 突变，在 3 个标本（13%）中观察到 ARID1A 突变，在 2 个标本（8%）中观察到 PIK3CA 突变，在 1 个标本（4%）中观察到 KRAS 突变，在 1 个标本（4%）中观察到 PTEN 突变，在 1 个标本（4%）中观察到 CTNNB1 突变，不包括同义突变。在鉴定出的突变中，TP53 中的 13 个突变、BRCA1 中的 10 个突变、BRCA2 中的 23 个突变位置中的 10 个突变、ARID1A 中的 7 个突变、PIK3CA 中的 1 个突变和 CTNNB1 中的 1 个突变与公共在线数据库中的报道一致；然而，其他鉴定出的突变是新的。原发性和复发性肿瘤配对标本的比较揭示了表达 RNA 中突变状态的变化。基于 RNA 测序的突变分析将有助于揭示卵巢癌中基因突变的种族差异，并了解基因突变对复发的贡献。
