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Pathway Mutations in Breast Cancer Using Whole-Exome Sequencing

The genomic landscape of breast cancer (BC) is complex. The purpose of this study was to decipher the mutational profiles of Taiwanese patients with BC using next-generation sequencing. We performed whole-exome sequencing on DNA from 24 tumor tissue specimens from BC patients. Sanger sequencing was...

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Autores principales: Chang, Ya-Sian, Chang, Chieh-Min, Lin, Chien-Yu, Chao, Dy-San, Huang, Hsi-Yuan, Chang, Jan-Gowth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cognizant Communication Corporation 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851574/
https://www.ncbi.nlm.nih.gov/pubmed/31575382
http://dx.doi.org/10.3727/096504019X15698362825407
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author Chang, Ya-Sian
Chang, Chieh-Min
Lin, Chien-Yu
Chao, Dy-San
Huang, Hsi-Yuan
Chang, Jan-Gowth
author_facet Chang, Ya-Sian
Chang, Chieh-Min
Lin, Chien-Yu
Chao, Dy-San
Huang, Hsi-Yuan
Chang, Jan-Gowth
author_sort Chang, Ya-Sian
collection PubMed
description The genomic landscape of breast cancer (BC) is complex. The purpose of this study was to decipher the mutational profiles of Taiwanese patients with BC using next-generation sequencing. We performed whole-exome sequencing on DNA from 24 tumor tissue specimens from BC patients. Sanger sequencing was used to validate the identified variants. Sanger sequencing was also performed on paired adjacent nontumor tissues. After genotype calling and algorithmic annotations, we identified 49 deleterious variants in canonical cancer-related genes in our BC cohort. The most frequently mutated genes were PIK3CA (16.67%), FKBP9 (12.5%), TP53 (12.5%), ATM (8.33%), CHEK2 (8.33%), FOXO3 (8.33%), NTRK1 (8.33%), and NUTM2B (8.33%). Seven mutated variants (ATR p.V1581fs, CSF1R p.R579Q, GATA3 p.T356delinsTMKS, LRP5 p.W389*, MAP3K1 p.T918fs, MET p.K1161fs, and MTR p.P1178S) were novel variants that are not present in any gene mutation database. After grouping the samples according to molecular subtype, we found that the cell cycle, MAPK, and chemokine signaling pathways in the luminal A subtype of BC; the focal adhesion, axon guidance, and endocytosis pathways in the luminal B subtype; and amyotrophic lateral sclerosis in the basal-like subtype were exclusively altered. Survival curve analysis showed that the presence of the MAPK signaling pathway and endocytosis mutations were correlated with a poor prognosis. These survival data were consistent with cBioPortal analyses of 2,051 BC cases. We discovered novel mutations in patients with BC. These results have implications for developing strategic, adjuvant, and gene-targeted therapies.
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spelling pubmed-78515742021-02-16 Pathway Mutations in Breast Cancer Using Whole-Exome Sequencing Chang, Ya-Sian Chang, Chieh-Min Lin, Chien-Yu Chao, Dy-San Huang, Hsi-Yuan Chang, Jan-Gowth Oncol Res Article The genomic landscape of breast cancer (BC) is complex. The purpose of this study was to decipher the mutational profiles of Taiwanese patients with BC using next-generation sequencing. We performed whole-exome sequencing on DNA from 24 tumor tissue specimens from BC patients. Sanger sequencing was used to validate the identified variants. Sanger sequencing was also performed on paired adjacent nontumor tissues. After genotype calling and algorithmic annotations, we identified 49 deleterious variants in canonical cancer-related genes in our BC cohort. The most frequently mutated genes were PIK3CA (16.67%), FKBP9 (12.5%), TP53 (12.5%), ATM (8.33%), CHEK2 (8.33%), FOXO3 (8.33%), NTRK1 (8.33%), and NUTM2B (8.33%). Seven mutated variants (ATR p.V1581fs, CSF1R p.R579Q, GATA3 p.T356delinsTMKS, LRP5 p.W389*, MAP3K1 p.T918fs, MET p.K1161fs, and MTR p.P1178S) were novel variants that are not present in any gene mutation database. After grouping the samples according to molecular subtype, we found that the cell cycle, MAPK, and chemokine signaling pathways in the luminal A subtype of BC; the focal adhesion, axon guidance, and endocytosis pathways in the luminal B subtype; and amyotrophic lateral sclerosis in the basal-like subtype were exclusively altered. Survival curve analysis showed that the presence of the MAPK signaling pathway and endocytosis mutations were correlated with a poor prognosis. These survival data were consistent with cBioPortal analyses of 2,051 BC cases. We discovered novel mutations in patients with BC. These results have implications for developing strategic, adjuvant, and gene-targeted therapies. Cognizant Communication Corporation 2020-03-27 /pmc/articles/PMC7851574/ /pubmed/31575382 http://dx.doi.org/10.3727/096504019X15698362825407 Text en Copyright © 2020 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License.
spellingShingle Article
Chang, Ya-Sian
Chang, Chieh-Min
Lin, Chien-Yu
Chao, Dy-San
Huang, Hsi-Yuan
Chang, Jan-Gowth
Pathway Mutations in Breast Cancer Using Whole-Exome Sequencing
title Pathway Mutations in Breast Cancer Using Whole-Exome Sequencing
title_full Pathway Mutations in Breast Cancer Using Whole-Exome Sequencing
title_fullStr Pathway Mutations in Breast Cancer Using Whole-Exome Sequencing
title_full_unstemmed Pathway Mutations in Breast Cancer Using Whole-Exome Sequencing
title_short Pathway Mutations in Breast Cancer Using Whole-Exome Sequencing
title_sort pathway mutations in breast cancer using whole-exome sequencing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851574/
https://www.ncbi.nlm.nih.gov/pubmed/31575382
http://dx.doi.org/10.3727/096504019X15698362825407
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