Comprehensive cohort analysis of mutational spectrum in early onset breast cancer patients
Journal
Cancers
Journal Volume
12
Journal Issue
8
Pages
1-17
Date Issued
2020
Author(s)
Midha M.K.
Huang Y.-F.
Yang H.-H.
Fan T.-C.
Chang N.-C.
Chen T.-H.
Wang Y.-T.
Shen C.-Y.
Yu A.L.
Chiu K.-P.
Chen C.-J.
Abstract
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. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
Early onset breast cancer (EOBC); Germline mutations; Missense mutations; Nonsynonymous mutations; Somatic mutations
SDGs
Other Subjects
protein p53; transcription factor GATA 3; adult; Article; breast cancer; cohort analysis; copy number variation; disease course; female; FLG gene; GATA3 gene; gene mutation; genetic code; genetic susceptibility; germline mutation; human; human cell; human tissue; KMT2C gene; KRT18 gene; leukocyte; major clinical study; missense mutation; MUC16 gene; MUC17 gene; NEBL gene; oncogene; pathogenesis; PIK3CA gene; prevalence; protein structure; somatic mutation; Taiwanese; TP53 gene; whole exome sequencing; whole genome sequencing
Publisher
MDPI AG
Type
journal article