Genomic characterization of Chinese ovarian clear cell carcinoma identifies driver genes by whole exome sequencing
| العنوان: | Genomic characterization of Chinese ovarian clear cell carcinoma identifies driver genes by whole exome sequencing |
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| المؤلفون: | Jun Ouyang, Weirong Fan, Xueli Zhang, Rong Zhang, Yuan Ren, Zhigang Zhang, Lining Cui, Tianjiao Luo, Fangliang Xing, Xuefeng Bai, Xin Xing, Huan Yi, Fengmian Wang, Cancan Zhang, Linyan Zhu, Qin Yang, Jianping Qiu, Pengcheng Jiang |
| المصدر: | Neoplasia (New York, N.Y.) Neoplasia: An International Journal for Oncology Research, Vol 22, Iss 9, Pp 399-430 (2020) |
| بيانات النشر: | Neoplasia Press, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Oncology, 0301 basic medicine, Cancer Research, ARID1A, medicine.disease_cause, 0302 clinical medicine, Tumor Cells, Cultured, Exome sequencing, Ovarian clear cell carcinomas, Ovarian Neoplasms, Medical record, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Clear cell carcinoma, MAGEE1, Female, KRAS, Target sequencing, Adult, medicine.medical_specialty, Original article, Biology, Malignancy, lcsh:RC254-282, Chromatin remodeling, 03 medical and health sciences, Asian People, Internal medicine, Exome Sequencing, medicine, Biomarkers, Tumor, PTEN, Humans, PI3K/AKT/mTOR pathway, Aged, Retrospective Studies, business.industry, Whole exome sequencing, Cancer, Driver mutation, medicine.disease, 030104 developmental biology, Case-Control Studies, Mutation, Cancer research, biology.protein, business, Biomedical sciences, Adenocarcinoma, Clear Cell, Follow-Up Studies |
| الوصف: | Background: Little is known about the genetic alterations characteristic of ovarian clear cell carcinoma (OCCC). Our aim was to identify targetable genomic alterations in this type of cancer. Methods: Forty-two OCCC formalin-fixed, paraffin-embedded (FFPE) tissue samples were analyzed by whole-exome sequencing (WES), and 74 FFPE tissue samples underwent targeted sequencing (TS) to confirm the relevant driver mutations. Cell proliferation was assessed by cell counting kit-8 (CCK8) assays. Findings: In the 42 samples, ARID1A (64.3%) and PIK3CA (28.5%) were frequently mutated, as were PPP2R1A (11.9%), PTEN (7.1%) and KRAS (4.8%), which have been reported in previous OCCC studies. We also detected mutations in MUC4 (28.6%), MAGEE1 (19%), and ARID3A (16.7%); associations with these genes have not been previously reported. The functional protein-activated pathways were associated with proliferation and survival (including the PI3K/AKT, TP53, and ERBB2 pathways) in 83% of OCCCs and with chromatin remodeling in 71% of OCCCs. Patients with alterations in MAGEE1 (64% in the targeted sequencing cohort) had worse clinical outcomes (log-rank p < 0.05). A functional study revealed that two MAGEE1 mutants, one lacking two MAGE domains and the other containing two MAGE domains, significantly decreased the proliferative capacity of OCCC cells. Funding: We successfully identified novel genetic alterations in OCCC using whole-exome sequencing and targeted sequencing of OCCC patient samples and potential therapeutic targets for the treatment of this malignancy. Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: The use of samples and medical records was approved by the research ethics committees of Shanghai University of Medicine & Health Sciences Affiliated with Sixth People’s Hospital South Campus (approval number: 2017-KY-01), Fujian Provincial Maternity and Children's Hospital (approval number: 2017049), Nanjing Medical University Affiliated with Changzhou Maternal and Child Health Care Hospital (approval number: 2017005), Nanjing Medical University Affiliated with Changzhou No. 2 People’s Hospital (approval number: 2016-017-01), and Nanjing Medical University Affiliated with Suzhou Municipal Hospital (approval number: L2017003). |
| اللغة: | English |
| تدمد: | 1476-5586 1522-8002 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b91d898e4feb659a83c42f0618a45b8dTest http://europepmc.org/articles/PMC7341065Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b91d898e4feb659a83c42f0618a45b8d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765586 15228002 |
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