Somatic gene mutation analysis of triple negative breast cancers

Breast. 2016 Oct:29:202-7. doi: 10.1016/j.breast.2016.06.018. Epub 2016 Jul 7.


Objectives: The aims of this study were to analyze triple negative breast cancer (TNBC) using an expanded next generation sequencing (NGS) assay, assess the clinical relevance using a recently described database, and correlate tumor morphology with detected genetic alterations.

Methods: DNA was isolated from twenty primary TNBCs and genes of interest were enriched and sequenced with hybrid capture, followed by variant detection and functional and clinical annotation. The JAX-CTP™ assay detects actionable variants in the form of single nucleotide variations, small insertions and deletions (≤50 bp), and copy number variants in 358 genes in specimens containing a neoplastic cell content of ≥50%. The JAX-CKB is a comprehensive database that curates tumor phenotype, genetic variant and protein effect, therapeutic relevance, and available treatment options.

Results: 18/20 (90%) of TNBCs contained at least one somatic mutation detected by the JAX-CTP™. MYC amplification was the most common alteration, present in 75% of tumors. TP53, AURKA, and KDR mutations were each present in 30% (6/20) of cases. Related recruiting clinical trials, extracted from JAX-CKB, included 166 for breast cancer, of which 17 were specific to only the TNBC subtype. All 17 trials were testing at least one therapy that targets a mutation identified in this sample set. The majority (89%) of tumors with basal-like histologic features had MYC amplification.

Conclusions: The expanded gene panel identified a variety of clinically actionable gene alterations in TNBCs. The identification of such variants increases the possibility for new therapeutic interventions and clinical trial eligibility for TNBC patients.

Keywords: Myc; Next generation sequencing; Triple negative breast cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aurora Kinase A / genetics
  • DNA, Neoplasm / isolation & purification
  • Female
  • Gene Amplification
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Middle Aged
  • Mutation*
  • Triple Negative Breast Neoplasms / genetics*
  • Tumor Suppressor Protein p53 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / genetics


  • DNA, Neoplasm
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • AURKA protein, human
  • Aurora Kinase A