title: Somatic gene mutation analysis of triple negative breast cancers.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, One Medical Center Drive, Lebanon, NH 03756, USA; Geisel School of Medicine, Hanover, NH, USA. Electronic address: Jessica.L.Dillon@hitchcock.org.
authors.forename: J L
authors.initials: JL
authors.lastname: Dillon
authors.affiliation: The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA. Electronic address: Susan.Mockus@jax.org.
authors.forename: S M
authors.initials: SM
authors.lastname: Mockus
authors.affiliation: The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA. Electronic address: Guru.Ananda@jax.org.
authors.forename: G
authors.initials: G
authors.lastname: Ananda
authors.affiliation: The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA. Electronic address: Vanessa.Spotlow@jax.org.
authors.forename: V
authors.initials: V
authors.lastname: Spotlow
authors.affiliation: Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, One Medical Center Drive, Lebanon, NH 03756, USA; Geisel School of Medicine, Hanover, NH, USA. Electronic address: Wendy.A.Wells@hitchcock.org.
authors.forename: W A
authors.initials: WA
authors.lastname: Wells
authors.affiliation: Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, One Medical Center Drive, Lebanon, NH 03756, USA; Geisel School of Medicine, Hanover, NH, USA; The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA. Electronic address: Gregory.J.Tsongalis@hitchcock.org.
authors.forename: G J
authors.initials: GJ
authors.lastname: Tsongalis
authors.affiliation: Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, One Medical Center Drive, Lebanon, NH 03756, USA; Geisel School of Medicine, Hanover, NH, USA. Electronic address: Jonathan.D.Marotti@hitchcock.org.
authors.forename: J D
authors.initials: JD
authors.lastname: Marotti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064096:Aurora Kinase A / Q000235:genetics; D004273:DNA, Neoplasm / Q000302:isolation & purification; D005260:Female; D005784:Gene Amplification; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D064726:Triple Negative Breast Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: Myc; Next generation sequencing; Triple negative breast cancer