Germline TP53 and MSH6 mutations implicated in sporadic triple-negative breast cancer (TNBC): a preliminary study
Abstract Background Germline BRCA1/2 prevalence is relatively low in sporadic triple-negative breast cancer (TNBC). We hypothesized that non-BRCA genes may also have significant germline contribution to Chinese sporadic TNBC, and the somatic mutational landscape of TNBC may vary between ethnic group...
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doaj-e6735064831f4408a1a4af82fb78ac632020-11-25T01:38:08ZengBMCHuman Genomics1479-73642019-01-011311910.1186/s40246-018-0186-yGermline TP53 and MSH6 mutations implicated in sporadic triple-negative breast cancer (TNBC): a preliminary studyDandan Yi0Lei Xu1Jiaqi Luo2Xiaobin You3Tao Huang4Yi Zi5Xiaoting Li6Ru Wang7Zaixuan Zhong8Xiaoqiao Tang9Ang Li10Yujian Shi11Jianmei Rao12Yifen Zhang13Jianfeng Sang14Department of General Surgery, Nanjing Drum Tower HospitalDepartment of General Surgery, Drum Tower Clinical Medical College of Nanjing Medical UniversityTop Gene Tech (Guangzhou) Co., Ltd.Top Gene Tech (Guangzhou) Co., Ltd.Department of Thyroid and Breast, Lianyungang First People’s HospitalTop Gene Tech (Guangzhou) Co., Ltd.Top Gene Tech (Guangzhou) Co., Ltd.Department of General Surgery, Drum Tower Clinical Medical College of Nanjing Medical UniversityTop Gene Tech (Guangzhou) Co., Ltd.Department of General Surgery, Nanjing Drum Tower HospitalTop Gene Tech (Guangzhou) Co., Ltd.Top Gene Tech (Guangzhou) Co., Ltd.Top Gene Tech (Guangzhou) Co., Ltd.Department of Pathology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese MedicineDepartment of General Surgery, Nanjing Drum Tower HospitalAbstract Background Germline BRCA1/2 prevalence is relatively low in sporadic triple-negative breast cancer (TNBC). We hypothesized that non-BRCA genes may also have significant germline contribution to Chinese sporadic TNBC, and the somatic mutational landscape of TNBC may vary between ethnic groups. We therefore conducted this study to investigate germline and somatic mutations in 43 cancer susceptibility genes in Chinese sporadic TNBC. Patients and methods Sixty-six Chinese sporadic TNBC patients were enrolled in this study. Germline and tumor DNA of each patient were subjected to capture-based next-generation sequencing using a 43-gene panel. Standard bioinformatic analysis and variant classification were performed to identify deleterious/likely deleterious germline mutations and somatic mutations. Mutational analysis was conducted to identify significantly mutated genes. Results Deleterious/likely deleterious germline mutations were identified in 27 (27/66, 40.9%) patients. Among the 27 patients, 9 (9/66, 13.6%) were TP53 carriers, 5 (5/66, 7.6%) were MSH6 carriers, and 5 (5/66, 7.6%) were BRCA1 carriers. Somatic mutations were identified in 64 (64/66, 97.0%) patients. TP53 somatic mutations occurred in most of the patients (45/66, 68.2%) and with highest mean allele frequency (28.1%), while NF1 and POLE were detected to have the highest mutation counts. Conclusions Our results supported our hypotheses and suggested great potentials of TP53 and MSH6 as novel candidates for TNBC predisposition genes. The high frequency of somatic NF1 and POLE mutations in this study showed possibilities for clinical benefits from androgen-blockade therapies and immunotherapies in Chinese TNBC patients. Our study indicated necessity of multi-gene testing for TNBC prevention and treatment.http://link.springer.com/article/10.1186/s40246-018-0186-yTP53MSH6NF1POLETNBCMulti-gene testing |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dandan Yi Lei Xu Jiaqi Luo Xiaobin You Tao Huang Yi Zi Xiaoting Li Ru Wang Zaixuan Zhong Xiaoqiao Tang Ang Li Yujian Shi Jianmei Rao Yifen Zhang Jianfeng Sang |
spellingShingle |
Dandan Yi Lei Xu Jiaqi Luo Xiaobin You Tao Huang Yi Zi Xiaoting Li Ru Wang Zaixuan Zhong Xiaoqiao Tang Ang Li Yujian Shi Jianmei Rao Yifen Zhang Jianfeng Sang Germline TP53 and MSH6 mutations implicated in sporadic triple-negative breast cancer (TNBC): a preliminary study Human Genomics TP53 MSH6 NF1 POLE TNBC Multi-gene testing |
author_facet |
Dandan Yi Lei Xu Jiaqi Luo Xiaobin You Tao Huang Yi Zi Xiaoting Li Ru Wang Zaixuan Zhong Xiaoqiao Tang Ang Li Yujian Shi Jianmei Rao Yifen Zhang Jianfeng Sang |
author_sort |
Dandan Yi |
title |
Germline TP53 and MSH6 mutations implicated in sporadic triple-negative breast cancer (TNBC): a preliminary study |
title_short |
Germline TP53 and MSH6 mutations implicated in sporadic triple-negative breast cancer (TNBC): a preliminary study |
title_full |
Germline TP53 and MSH6 mutations implicated in sporadic triple-negative breast cancer (TNBC): a preliminary study |
title_fullStr |
Germline TP53 and MSH6 mutations implicated in sporadic triple-negative breast cancer (TNBC): a preliminary study |
title_full_unstemmed |
Germline TP53 and MSH6 mutations implicated in sporadic triple-negative breast cancer (TNBC): a preliminary study |
title_sort |
germline tp53 and msh6 mutations implicated in sporadic triple-negative breast cancer (tnbc): a preliminary study |
publisher |
BMC |
series |
Human Genomics |
issn |
1479-7364 |
publishDate |
2019-01-01 |
description |
Abstract Background Germline BRCA1/2 prevalence is relatively low in sporadic triple-negative breast cancer (TNBC). We hypothesized that non-BRCA genes may also have significant germline contribution to Chinese sporadic TNBC, and the somatic mutational landscape of TNBC may vary between ethnic groups. We therefore conducted this study to investigate germline and somatic mutations in 43 cancer susceptibility genes in Chinese sporadic TNBC. Patients and methods Sixty-six Chinese sporadic TNBC patients were enrolled in this study. Germline and tumor DNA of each patient were subjected to capture-based next-generation sequencing using a 43-gene panel. Standard bioinformatic analysis and variant classification were performed to identify deleterious/likely deleterious germline mutations and somatic mutations. Mutational analysis was conducted to identify significantly mutated genes. Results Deleterious/likely deleterious germline mutations were identified in 27 (27/66, 40.9%) patients. Among the 27 patients, 9 (9/66, 13.6%) were TP53 carriers, 5 (5/66, 7.6%) were MSH6 carriers, and 5 (5/66, 7.6%) were BRCA1 carriers. Somatic mutations were identified in 64 (64/66, 97.0%) patients. TP53 somatic mutations occurred in most of the patients (45/66, 68.2%) and with highest mean allele frequency (28.1%), while NF1 and POLE were detected to have the highest mutation counts. Conclusions Our results supported our hypotheses and suggested great potentials of TP53 and MSH6 as novel candidates for TNBC predisposition genes. The high frequency of somatic NF1 and POLE mutations in this study showed possibilities for clinical benefits from androgen-blockade therapies and immunotherapies in Chinese TNBC patients. Our study indicated necessity of multi-gene testing for TNBC prevention and treatment. |
topic |
TP53 MSH6 NF1 POLE TNBC Multi-gene testing |
url |
http://link.springer.com/article/10.1186/s40246-018-0186-y |
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