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Comprehensive genomic profiling of high‐grade serous ovarian carcinoma from Chinese patients identifies co‐occurring mutations in the Ras/Raf pathway with TP53

High‐grade serous ovarian carcinoma (HGSOC) is a major form of ovarian epithelial tumor that is often diagnosed only at an advanced stage when it is already highly aggressive. We performed comprehensive genomic profiling using an analytically validated clinical next‐generation sequencing assay to id...

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Autores principales: Zhong, Fangfang, Zhu, Tao, Pan, Xuedong, Zhang, Yanling, Yang, Haikun, Wang, Xiangping, Hu, Jinwei, Han, Hongxia, Mei, Lei, Chen, Donglin, Wang, Kai, Zhou, Xianrong, Li, Xiuqin, Dong, Xiaowei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639185/
https://www.ncbi.nlm.nih.gov/pubmed/31124283
http://dx.doi.org/10.1002/cam4.2243
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author Zhong, Fangfang
Zhu, Tao
Pan, Xuedong
Zhang, Yanling
Yang, Haikun
Wang, Xiangping
Hu, Jinwei
Han, Hongxia
Mei, Lei
Chen, Donglin
Wang, Kai
Zhou, Xianrong
Li, Xiuqin
Dong, Xiaowei
author_facet Zhong, Fangfang
Zhu, Tao
Pan, Xuedong
Zhang, Yanling
Yang, Haikun
Wang, Xiangping
Hu, Jinwei
Han, Hongxia
Mei, Lei
Chen, Donglin
Wang, Kai
Zhou, Xianrong
Li, Xiuqin
Dong, Xiaowei
author_sort Zhong, Fangfang
collection PubMed
description High‐grade serous ovarian carcinoma (HGSOC) is a major form of ovarian epithelial tumor that is often diagnosed only at an advanced stage when it is already highly aggressive. We performed comprehensive genomic profiling using an analytically validated clinical next‐generation sequencing assay to identify genomic alterations in 450 cancer‐related genes in a cohort of 88 Chinese HGSOC patients. Overall, we detected 547 genomic alterations with an average of 6.2 alterations per tumor. Most of these HGSOC tumors had low tumor mutation burden and were microsatellite stable. Consistent with earlier studies, TP53 mutations were present in the majority (96.6%) of the tumors studied, and mutations in BRCA1/2 that affect DNA repair were also detected frequently in 20.5% of the tumors. However, we observed a 10.2% of mutated genes in the Ras/Raf pathway, all co‐occurring with TP53 mutations in the same tumor, which was unrecognized previously. Our results show that in HGSOC patients, there may be an unrecognized co‐occurrence of TP53 mutations with mutations in Ras/Raf pathway.
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spelling pubmed-66391852019-07-29 Comprehensive genomic profiling of high‐grade serous ovarian carcinoma from Chinese patients identifies co‐occurring mutations in the Ras/Raf pathway with TP53 Zhong, Fangfang Zhu, Tao Pan, Xuedong Zhang, Yanling Yang, Haikun Wang, Xiangping Hu, Jinwei Han, Hongxia Mei, Lei Chen, Donglin Wang, Kai Zhou, Xianrong Li, Xiuqin Dong, Xiaowei Cancer Med Cancer Biology High‐grade serous ovarian carcinoma (HGSOC) is a major form of ovarian epithelial tumor that is often diagnosed only at an advanced stage when it is already highly aggressive. We performed comprehensive genomic profiling using an analytically validated clinical next‐generation sequencing assay to identify genomic alterations in 450 cancer‐related genes in a cohort of 88 Chinese HGSOC patients. Overall, we detected 547 genomic alterations with an average of 6.2 alterations per tumor. Most of these HGSOC tumors had low tumor mutation burden and were microsatellite stable. Consistent with earlier studies, TP53 mutations were present in the majority (96.6%) of the tumors studied, and mutations in BRCA1/2 that affect DNA repair were also detected frequently in 20.5% of the tumors. However, we observed a 10.2% of mutated genes in the Ras/Raf pathway, all co‐occurring with TP53 mutations in the same tumor, which was unrecognized previously. Our results show that in HGSOC patients, there may be an unrecognized co‐occurrence of TP53 mutations with mutations in Ras/Raf pathway. John Wiley and Sons Inc. 2019-05-24 /pmc/articles/PMC6639185/ /pubmed/31124283 http://dx.doi.org/10.1002/cam4.2243 Text en © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Zhong, Fangfang
Zhu, Tao
Pan, Xuedong
Zhang, Yanling
Yang, Haikun
Wang, Xiangping
Hu, Jinwei
Han, Hongxia
Mei, Lei
Chen, Donglin
Wang, Kai
Zhou, Xianrong
Li, Xiuqin
Dong, Xiaowei
Comprehensive genomic profiling of high‐grade serous ovarian carcinoma from Chinese patients identifies co‐occurring mutations in the Ras/Raf pathway with TP53
title Comprehensive genomic profiling of high‐grade serous ovarian carcinoma from Chinese patients identifies co‐occurring mutations in the Ras/Raf pathway with TP53
title_full Comprehensive genomic profiling of high‐grade serous ovarian carcinoma from Chinese patients identifies co‐occurring mutations in the Ras/Raf pathway with TP53
title_fullStr Comprehensive genomic profiling of high‐grade serous ovarian carcinoma from Chinese patients identifies co‐occurring mutations in the Ras/Raf pathway with TP53
title_full_unstemmed Comprehensive genomic profiling of high‐grade serous ovarian carcinoma from Chinese patients identifies co‐occurring mutations in the Ras/Raf pathway with TP53
title_short Comprehensive genomic profiling of high‐grade serous ovarian carcinoma from Chinese patients identifies co‐occurring mutations in the Ras/Raf pathway with TP53
title_sort comprehensive genomic profiling of high‐grade serous ovarian carcinoma from chinese patients identifies co‐occurring mutations in the ras/raf pathway with tp53
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639185/
https://www.ncbi.nlm.nih.gov/pubmed/31124283
http://dx.doi.org/10.1002/cam4.2243
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