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Chromosome instability region analysis and identification of the driver genes of the epithelial ovarian cancer cell lines A2780 and SKOV3 |
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| Authors: | Jianxiong Li Zexin Chen Wentao Xiao Huaguo Liang Yanan Liu Wenqi Hao Yongli Zhang Fengxiang Wei |
| Institution: | 1. Department of Gynecology, Longgang District Maternity and Child Healthcare Hospital of Shenzhen City (Longgang Maternity and Child Institute of Shantou University Medical College), Shenzhen, China
Contribution: Funding acquisition (equal), Project administration (equal);2. Department of Cell Biology and Medical Genetics, School of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou, China Contribution: Methodology (equal), Visualization (equal);3. Department of Gynecology, Longgang District Maternity and Child Healthcare Hospital of Shenzhen City (Longgang Maternity and Child Institute of Shantou University Medical College), Shenzhen, China Contribution: Software (equal), Writing - review & editing (equal);4. Department of Cell Biology and Medical Genetics, School of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou, China Contribution: Formal analysis (equal), Methodology (equal);5. The Genetics Laboratory, Longgang District Maternity and Child Healthcare Hospital of Shenzhen City (Longgang Maternity and Child Institute of Shantou University Medical College), Shenzhen, China Contribution: Writing - review & editing (equal);6. The Genetics Laboratory, Longgang District Maternity and Child Healthcare Hospital of Shenzhen City (Longgang Maternity and Child Institute of Shantou University Medical College), Shenzhen, China Contribution: Software (equal);7. Department of Cell Biology and Medical Genetics, School of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou, China;8. The Genetics Laboratory, Longgang District Maternity and Child Healthcare Hospital of Shenzhen City (Longgang Maternity and Child Institute of Shantou University Medical College), Shenzhen, China |
| Abstract: | Epithelial ovarian cancer (EOC) is one of the most prevalent gynaecological cancers worldwide. The molecular mechanisms of serous ovarian cancer (SOC) remain unclear and not well understood. SOC cases are primarily diagnosed at the late stage, resulting in a poor prognosis. Advances in molecular biology techniques allow us to obtain a better understanding of precise molecular mechanisms and to identify the chromosome instability region and key driver genes in the carcinogenesis and progression of SOC. Whole-exome sequencing was performed on the normal ovarian cell line IOSE80 and the EOC cell lines SKOV3 and A2780. The single-nucleotide variation burden, distribution, frequency and signature followed the known ovarian mutation profiles, without chromosomal bias. Recurrently mutated ovarian cancer driver genes, including LRP1B, KMT2A, ARID1A, KMT2C and ATRX were also found in two cell lines. The genome distribution of copy number alterations was found by copy number variation (CNV) analysis, including amplification of 17q12 and 4p16.1 and deletion of 10q23.33. The CNVs of MED1, GRB7 and MIEN1 located at 17q12 were found to be correlated with the overall survival of SOC patients (MED1: p = 0.028, GRB7: p = 0.0048, MIEN1: p = 0.0051), and the expression of the three driver genes in the ovarian cell line IOSE80 and EOC cell lines SKOV3 and A2780 was confirmed by western blot and cell immunohistochemistry. |
| Keywords: | copy number variation driver gene serous ovarian cancer single-nucleotide variation whole-exome sequencing |