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Genomic characterization of Chinese ovarian clear cell carcinoma identifies driver genes by whole exome sequencing

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. Forty-two OCCC formalin-fixed, paraffin-embedded (FFPE) tissue samples were analyzed by whole-exome sequencing (WES), an...

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Autores principales: Yang, Qin, Zhang, Cancan, Ren, Yuan, Yi, Huan, Luo, Tianjiao, Xing, Fangliang, Bai, Xuefeng, Cui, Lining, Zhu, Linyan, Ouyang, Jun, Jiang, Pengcheng, Fan, Weirong, Qiu, Jianping, Wang, Fengmian, Xing, Xin, Zhang, Zhigang, Zhang, Xueli, Zhang, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341065/
https://www.ncbi.nlm.nih.gov/pubmed/32650224
http://dx.doi.org/10.1016/j.neo.2020.06.002
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author Yang, Qin
Zhang, Cancan
Ren, Yuan
Yi, Huan
Luo, Tianjiao
Xing, Fangliang
Bai, Xuefeng
Cui, Lining
Zhu, Linyan
Ouyang, Jun
Jiang, Pengcheng
Fan, Weirong
Qiu, Jianping
Wang, Fengmian
Xing, Xin
Zhang, Zhigang
Zhang, Xueli
Zhang, Rong
author_facet Yang, Qin
Zhang, Cancan
Ren, Yuan
Yi, Huan
Luo, Tianjiao
Xing, Fangliang
Bai, Xuefeng
Cui, Lining
Zhu, Linyan
Ouyang, Jun
Jiang, Pengcheng
Fan, Weirong
Qiu, Jianping
Wang, Fengmian
Xing, Xin
Zhang, Zhigang
Zhang, Xueli
Zhang, Rong
author_sort Yang, Qin
collection PubMed
description 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. 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. 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. 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.
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spelling pubmed-73410652020-07-14 Genomic characterization of Chinese ovarian clear cell carcinoma identifies driver genes by whole exome sequencing Yang, Qin Zhang, Cancan Ren, Yuan Yi, Huan Luo, Tianjiao Xing, Fangliang Bai, Xuefeng Cui, Lining Zhu, Linyan Ouyang, Jun Jiang, Pengcheng Fan, Weirong Qiu, Jianping Wang, Fengmian Xing, Xin Zhang, Zhigang Zhang, Xueli Zhang, Rong Neoplasia Original article 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. 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. 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. 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. Neoplasia Press 2020-07-07 /pmc/articles/PMC7341065/ /pubmed/32650224 http://dx.doi.org/10.1016/j.neo.2020.06.002 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Yang, Qin
Zhang, Cancan
Ren, Yuan
Yi, Huan
Luo, Tianjiao
Xing, Fangliang
Bai, Xuefeng
Cui, Lining
Zhu, Linyan
Ouyang, Jun
Jiang, Pengcheng
Fan, Weirong
Qiu, Jianping
Wang, Fengmian
Xing, Xin
Zhang, Zhigang
Zhang, Xueli
Zhang, Rong
Genomic characterization of Chinese ovarian clear cell carcinoma identifies driver genes by whole exome sequencing
title Genomic characterization of Chinese ovarian clear cell carcinoma identifies driver genes by whole exome sequencing
title_full Genomic characterization of Chinese ovarian clear cell carcinoma identifies driver genes by whole exome sequencing
title_fullStr Genomic characterization of Chinese ovarian clear cell carcinoma identifies driver genes by whole exome sequencing
title_full_unstemmed Genomic characterization of Chinese ovarian clear cell carcinoma identifies driver genes by whole exome sequencing
title_short Genomic characterization of Chinese ovarian clear cell carcinoma identifies driver genes by whole exome sequencing
title_sort genomic characterization of chinese ovarian clear cell carcinoma identifies driver genes by whole exome sequencing
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341065/
https://www.ncbi.nlm.nih.gov/pubmed/32650224
http://dx.doi.org/10.1016/j.neo.2020.06.002
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