Cargando…
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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783436413579034624 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6639185 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhongfangfang comprehensivegenomicprofilingofhighgradeserousovariancarcinomafromchinesepatientsidentifiescooccurringmutationsintherasrafpathwaywithtp53 AT zhutao comprehensivegenomicprofilingofhighgradeserousovariancarcinomafromchinesepatientsidentifiescooccurringmutationsintherasrafpathwaywithtp53 AT panxuedong comprehensivegenomicprofilingofhighgradeserousovariancarcinomafromchinesepatientsidentifiescooccurringmutationsintherasrafpathwaywithtp53 AT zhangyanling comprehensivegenomicprofilingofhighgradeserousovariancarcinomafromchinesepatientsidentifiescooccurringmutationsintherasrafpathwaywithtp53 AT yanghaikun comprehensivegenomicprofilingofhighgradeserousovariancarcinomafromchinesepatientsidentifiescooccurringmutationsintherasrafpathwaywithtp53 AT wangxiangping comprehensivegenomicprofilingofhighgradeserousovariancarcinomafromchinesepatientsidentifiescooccurringmutationsintherasrafpathwaywithtp53 AT hujinwei comprehensivegenomicprofilingofhighgradeserousovariancarcinomafromchinesepatientsidentifiescooccurringmutationsintherasrafpathwaywithtp53 AT hanhongxia comprehensivegenomicprofilingofhighgradeserousovariancarcinomafromchinesepatientsidentifiescooccurringmutationsintherasrafpathwaywithtp53 AT meilei comprehensivegenomicprofilingofhighgradeserousovariancarcinomafromchinesepatientsidentifiescooccurringmutationsintherasrafpathwaywithtp53 AT chendonglin comprehensivegenomicprofilingofhighgradeserousovariancarcinomafromchinesepatientsidentifiescooccurringmutationsintherasrafpathwaywithtp53 AT wangkai comprehensivegenomicprofilingofhighgradeserousovariancarcinomafromchinesepatientsidentifiescooccurringmutationsintherasrafpathwaywithtp53 AT zhouxianrong comprehensivegenomicprofilingofhighgradeserousovariancarcinomafromchinesepatientsidentifiescooccurringmutationsintherasrafpathwaywithtp53 AT lixiuqin comprehensivegenomicprofilingofhighgradeserousovariancarcinomafromchinesepatientsidentifiescooccurringmutationsintherasrafpathwaywithtp53 AT dongxiaowei comprehensivegenomicprofilingofhighgradeserousovariancarcinomafromchinesepatientsidentifiescooccurringmutationsintherasrafpathwaywithtp53 |