Pathway Mutations in Breast Cancer Using Whole-Exome Sequencing

Oncol Res. 2020 Mar 27;28(2):107-116. doi: 10.3727/096504019X15698362825407. Epub 2019 Oct 1.


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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / classification
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Exome Sequencing
  • Female
  • Genotype
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / isolation & purification
  • Prognosis*
  • Signal Transduction / genetics


  • Neoplasm Proteins