Somatic gene mutation analysis of triple negative breast cancers.
Document Type
Article
Publication Date
10-2016
JAX Location
Reprint Collection
JAX Source
Breast 2016 Oct; 29:202-7.
Volume
29
First Page
202
Last Page
207
ISSN
1532-3080
PMID
27397723
Abstract
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.
Breast 2016 Oct; 29:202-7.
Recommended Citation
Dillon J,
Mockus S,
Ananda G,
Spotlow V,
Wells W,
Tsongalis G,
Marotti J.
Somatic gene mutation analysis of triple negative breast cancers. Breast 2016 Oct; 29:202-7.