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.

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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.

J Mol Diagn. 2018 Dec 18;:

Authors: Gupta S, Vanderbilt CM, Cotzia P, Arias Stella JA, Chang JC, Zehir A, Benayed R, Nafa K, Razavi P, Hyman DM, Baselga J, Berger MF, Ladanyi M, Arcila ME, Ross DS

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 post-chemotherapy, 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, we determined the frequency of these alterations. A total of 5,399 cases were included in the study. This encompassed 2,890 institutional cases tested by the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets assay and 2,509 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 of 5399 cases), and showed a greater than 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.

PMID: 30576871 [PubMed - as supplied by publisher]

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