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Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients

Early onset breast cancer (EOBC), diagnosed at age ~40 or younger, is associated with a poorer prognosis and higher mortality rate compared to breast cancer diagnosed at age 50 or older. EOBC poses a serious threat to public health and requires in-depth investigation. We studied a cohort comprising...

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Autores principales: Midha, Mohit K., Huang, Yu-Feng, Yang, Hsiao-Hsiang, Fan, Tan-Chi, Chang, Nai-Chuan, Chen, Tzu-Han, Wang, Yu-Tai, Kuo, Wen-Hung, Chang, King-Jen, Shen, Chen-Yang, Yu, Alice L., Chiu, Kuo-Ping, Chen, Chien-Jen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464007/
https://www.ncbi.nlm.nih.gov/pubmed/32731431
http://dx.doi.org/10.3390/cancers12082089
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author Midha, Mohit K.
Huang, Yu-Feng
Yang, Hsiao-Hsiang
Fan, Tan-Chi
Chang, Nai-Chuan
Chen, Tzu-Han
Wang, Yu-Tai
Kuo, Wen-Hung
Chang, King-Jen
Shen, Chen-Yang
Yu, Alice L.
Chiu, Kuo-Ping
Chen, Chien-Jen
author_facet Midha, Mohit K.
Huang, Yu-Feng
Yang, Hsiao-Hsiang
Fan, Tan-Chi
Chang, Nai-Chuan
Chen, Tzu-Han
Wang, Yu-Tai
Kuo, Wen-Hung
Chang, King-Jen
Shen, Chen-Yang
Yu, Alice L.
Chiu, Kuo-Ping
Chen, Chien-Jen
author_sort Midha, Mohit K.
collection PubMed
description Early onset breast cancer (EOBC), diagnosed at age ~40 or younger, is associated with a poorer prognosis and higher mortality rate compared to breast cancer diagnosed at age 50 or older. EOBC poses a serious threat to public health and requires in-depth investigation. We studied a cohort comprising 90 Taiwanese female patients, aiming to unravel the underlying mechanisms of EOBC etiopathogenesis. Sequence data generated by whole-exome sequencing (WES) and whole-genome sequencing (WGS) from white blood cell (WBC)–tumor pairs were analyzed to identify somatic missense mutations, copy number variations (CNVs) and germline missense mutations. Similar to regular breast cancer, the key somatic mutation-susceptibility genes of EOBC include TP53 (40% prevalence), PIK3CA (37%), GATA3 (17%) and KMT2C (17%), which are frequently reported in breast cancer; however, the structural protein-coding genes MUC17 (19%), FLG (16%) and NEBL (11%) show a significantly higher prevalence in EOBC. Furthermore, the top 2 genes harboring EOBC germline mutations, MUC16 (19%) and KRT18 (19%), encode structural proteins. Compared to conventional breast cancer, an unexpectedly higher number of EOBC susceptibility genes encode structural proteins. We suspect that mutations in structural proteins may increase physical permeability to environmental hormones and carcinogens and cause breast cancer to occur at a young age.
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spelling pubmed-74640072020-09-04 Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients Midha, Mohit K. Huang, Yu-Feng Yang, Hsiao-Hsiang Fan, Tan-Chi Chang, Nai-Chuan Chen, Tzu-Han Wang, Yu-Tai Kuo, Wen-Hung Chang, King-Jen Shen, Chen-Yang Yu, Alice L. Chiu, Kuo-Ping Chen, Chien-Jen Cancers (Basel) Article Early onset breast cancer (EOBC), diagnosed at age ~40 or younger, is associated with a poorer prognosis and higher mortality rate compared to breast cancer diagnosed at age 50 or older. EOBC poses a serious threat to public health and requires in-depth investigation. We studied a cohort comprising 90 Taiwanese female patients, aiming to unravel the underlying mechanisms of EOBC etiopathogenesis. Sequence data generated by whole-exome sequencing (WES) and whole-genome sequencing (WGS) from white blood cell (WBC)–tumor pairs were analyzed to identify somatic missense mutations, copy number variations (CNVs) and germline missense mutations. Similar to regular breast cancer, the key somatic mutation-susceptibility genes of EOBC include TP53 (40% prevalence), PIK3CA (37%), GATA3 (17%) and KMT2C (17%), which are frequently reported in breast cancer; however, the structural protein-coding genes MUC17 (19%), FLG (16%) and NEBL (11%) show a significantly higher prevalence in EOBC. Furthermore, the top 2 genes harboring EOBC germline mutations, MUC16 (19%) and KRT18 (19%), encode structural proteins. Compared to conventional breast cancer, an unexpectedly higher number of EOBC susceptibility genes encode structural proteins. We suspect that mutations in structural proteins may increase physical permeability to environmental hormones and carcinogens and cause breast cancer to occur at a young age. MDPI 2020-07-28 /pmc/articles/PMC7464007/ /pubmed/32731431 http://dx.doi.org/10.3390/cancers12082089 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Midha, Mohit K.
Huang, Yu-Feng
Yang, Hsiao-Hsiang
Fan, Tan-Chi
Chang, Nai-Chuan
Chen, Tzu-Han
Wang, Yu-Tai
Kuo, Wen-Hung
Chang, King-Jen
Shen, Chen-Yang
Yu, Alice L.
Chiu, Kuo-Ping
Chen, Chien-Jen
Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients
title Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients
title_full Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients
title_fullStr Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients
title_full_unstemmed Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients
title_short Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients
title_sort comprehensive cohort analysis of mutational spectrum in early onset breast cancer patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464007/
https://www.ncbi.nlm.nih.gov/pubmed/32731431
http://dx.doi.org/10.3390/cancers12082089
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