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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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2020
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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. |
format | Online Article Text |
id | pubmed-7341065 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
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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