Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients
Mohit K Midha1,2, Yu-Feng Huang1, Hsiao-Hsiang Yang3
1Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
Cancers
|August 1, 2020
Summary
Early onset breast cancer (EOBC) in Taiwanese women shows distinct genetic patterns, with a higher prevalence of mutations in structural protein genes. These findings suggest structural protein alterations may contribute to the early development of breast cancer.
Area of Science:
- Genomics
- Oncology
- Molecular Biology
Background:
- Early onset breast cancer (EOBC), diagnosed before age 40, presents a poorer prognosis and higher mortality than later-onset breast cancer.
- EOBC represents a significant public health concern necessitating detailed etiological investigation.
Purpose of the Study:
- To investigate the genetic underpinnings of early onset breast cancer (EOBC) in a Taiwanese female cohort.
- To identify key somatic and germline mutations associated with EOBC pathogenesis.
Main Methods:
- Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were performed on white blood cell (WBC)-tumor pairs from 90 Taiwanese female EOBC patients.
- Analysis focused on identifying somatic missense mutations, copy number variations (CNVs), and germline missense mutations.
Main Results:
- Common breast cancer genes like TP53 and PIK3CA were mutated in EOBC, but MUC17, FLG, and NEBL showed significantly higher prevalence.
- Germline mutations in MUC16 and KRT18 were identified as top hits in EOBC.
- A notable proportion of EOBC susceptibility genes identified encode structural proteins, exceeding expectations compared to conventional breast cancer.
Conclusions:
- EOBC exhibits a unique genetic landscape with a disproportionately high number of mutations in structural protein-coding genes.
- Mutations in structural proteins might enhance susceptibility to environmental carcinogens and hormones, potentially driving early breast cancer development.
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