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

Somatic gene mutation analysis of triple negative breast cancers.

Author information

1
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.
2
The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA. Electronic address: Susan.Mockus@jax.org.
3
The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA. Electronic address: Guru.Ananda@jax.org.
4
The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA. Electronic address: Vanessa.Spotlow@jax.org.
5
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.
6
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.
7
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.

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.

KEYWORDS:

Myc; Next generation sequencing; Triple negative breast cancer

PMID:
27397723
DOI:
10.1016/j.breast.2016.06.018
[Indexed for MEDLINE]

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