title: A novel somatic MAPK1 mutation in primary ovarian mixed germ cell tumors.
abstract: 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 α (PPP2R1A), ring finger protein 43 (RNF43), DNA directed polymerase ε (POLE1), ribonuclease type III (DICER1), CCCTC‑binding factor (CTCF), ribosomal protein L22 (RPL22), DNA methyltransferase 3α (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.
authors.affiliation: Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.affiliation: Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pathology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Yu
authors.affiliation: Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Fa-Ying
authors.initials: FY
authors.lastname: Liu
authors.affiliation: Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Bi-Cheng
authors.initials: BC
authors.lastname: Yang
authors.affiliation: Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Mei-Zhen
authors.initials: MZ
authors.lastname: Huang
authors.affiliation: Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Jiu-Bai
authors.initials: JB
authors.lastname: Guo
authors.affiliation: Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Qiu-Hua
authors.initials: QH
authors.lastname: Xie
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: He
authors.affiliation: Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Ou-Ping
authors.initials: OP
authors.lastname: Huang
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics*; D009154:Mutation; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1