Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma.
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, α) 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.
Key Laboratory of Women's Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China; Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China.
Yang
Y
Zou
Key Laboratory of Women's Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China; Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China.
Fa-Ying
FY
Liu
Key Laboratory of Women's Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China; Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China.
Huai
H
Liu
Key Laboratory of Women's Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China; Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China.
Feng
F
Wang
Key Laboratory of Women's Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China; Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China; Graduate School of Nanchang University, Nanchang, Jiangxi 330031, China.
Wei
W
Li
Graduate School of Nanchang University, Nanchang, Jiangxi 330031, China; Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029, China.
Mei-Zhen
MZ
Huang
Key Laboratory of Women's Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China; Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China; Graduate School of Nanchang University, Nanchang, Jiangxi 330031, China.
Yan
Y
Huang
Key Laboratory of Women's Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China; Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China; Graduate School of Nanchang University, Nanchang, Jiangxi 330031, China.
Xiao-Qun
XQ
Yuan
Graduate School of Nanchang University, Nanchang, Jiangxi 330031, China; Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029, China.
Xiao-Yun
XY
Xu
Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029, China. Electronic address: huangouping@gmail.com.
Ou-Ping
OP
Huang
Department of Pharmacology & Molecular Therapeutics, Nanchang University School of Pharmaceutical Science, Nanchang 330006, China. Electronic address: jxhm56@hotmail.com.
Ming
M
He
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D018269:Carcinoma, Endometrioid / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D002648:Child; D002675:Child, Preschool; D004257:DNA Polymerase II / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D016415:Sequence Alignment; D055815:Young Adult
D000075223:Poly-ADP-Ribose Binding Proteins; D004257:DNA Polymerase II; C119525:POLE protein, human
Chinese; Mutation; Ovarian endometrioid carcinoma; POLE1