Identification of novel mutations of ovarian cancer-related genes from RNA-sequencing data for Japanese epithelial ovarian cancer patients.

Abstract

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.

• Authors: Saya Nagasawa, Kazuhiro Ikeda, Kuniko Horie-Inoue, Sho Sato, Satoru Takeda, Kosei Hasegawa, Satoshi Inoue
• Journal: Endocrine journal (Endocr J) Vol. 67 Issue 2 Pg. 219-229 (Feb 28 2020) ISSN: 1348-4540 [Electronic] Japan
• PMID: 31748433 (Publication Type: Journal Article)

Chemical References

• ARID1A protein, human
• BRCA1 Protein
• BRCA1 protein, human
• BRCA2 Protein
• BRCA2 protein, human
• CTNNB1 protein, human
• DNA-Binding Proteins
• KRAS protein, human
• TP53 protein, human
• Transcription Factors
• Tumor Suppressor Protein p53
• beta Catenin
• Class I Phosphatidylinositol 3-Kinases
• PIK3CA protein, human
• PTEN Phosphohydrolase
• PTEN protein, human
• Proto-Oncogene Proteins p21(ras)

Topics

• Adenocarcinoma, Clear Cell (genetics)
• Asian People (genetics)
• BRCA1 Protein (genetics)
• BRCA2 Protein (genetics)
• Carcinoma, Endometrioid (genetics)
• Carcinoma, Ovarian Epithelial (genetics)
• Class I Phosphatidylinositol 3-Kinases (genetics)
• DNA-Binding Proteins (genetics)
• Female
• Humans
• Japan
• Mutation
• Neoplasm Recurrence, Local (genetics)
• Neoplasms, Cystic, Mucinous, and Serous (genetics)
• Ovarian Neoplasms (genetics)
• PTEN Phosphohydrolase (genetics)
• Proto-Oncogene Proteins p21(ras) (genetics)
• Sequence Analysis, RNA
• Transcription Factors (genetics)
• Tumor Suppressor Protein p53 (genetics)
• beta Catenin (genetics)