Next-Generation Sequencing-Based Assessment of JAK2, PD-L1, and PD-L2 Copy Number Alterations at 9p24.1 in Breast Cancer: Potential Implications for Clinical Management. Academic Article uri icon

Overview

abstract

  • Genomic amplification at 9p24.1, including the loci for JAK2, PD-L1, and PD-L2, has recently been described as a mechanism of resistance in postchemotherapy, triple-negative breast cancer. This genomic signature holds significant promise as a prognostic biomarker and has implications for targeted therapy with JAK2 inhibitors, as well as with immunotherapy. To guide future screening strategies, the frequency of these alterations was determined. A total of 5399 cases were included in the study. This encompassed 2890 institutional cases tested by the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets assay and 2509 cases from The Cancer Genome Atlas (TCGA). The combined incidence of 9p24.1 amplifications in both the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets and TCGA cohorts was 1.0% (56/5399 cases) and showed a >10-fold higher incidence in triple-negative breast cancer (triple-negative: 5.1%; non-triple-negative: 0.5%). Tumor mutation burden and stromal tumor infiltrating lymphocytes, parameters used to assess response to immunotherapy, were not significantly higher for these cases. The significance of genomic losses at 9p24.1 is unclear, and further studies are needed. Herein, we studied the spectrum of copy number alterations in breast cancer cases within our institutional clinical sequencing cohort and those profiled by TCGA to determine the frequency of genomic alterations that may predict response or resistance to JAK2 inhibitors and/or immunotherapy.

publication date

  • December 18, 2018

Research

keywords

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • DNA Copy Number Variations
  • High-Throughput Nucleotide Sequencing
  • Janus Kinase 2
  • Programmed Cell Death 1 Ligand 2 Protein
  • Triple Negative Breast Neoplasms

Identity

PubMed Central ID

  • PMC6432425

Scopus Document Identifier

  • 85062056273

Digital Object Identifier (DOI)

  • 10.1016/j.jmoldx.2018.10.006

PubMed ID

  • 30576871

Additional Document Info

volume

  • 21

issue

  • 2