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 Journal Article


Authors: Gupta, S.; Vanderbilt, C. M.; Cotzia, P.; Arias-Stella, J. A. 3rd; Chang, J. C.; Zehir, A.; Benayed, R.; Nafa, K.; Razavi, P.; Hyman, D. M.; Baselga, J.; Berger, M. F.; Ladanyi, M.; Arcila, M. E.; Ross, D. S.
Article Title: 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
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. © 2019 American Society for Investigative Pathology and the Association for Molecular Pathology
Keywords: immunohistochemistry; adult; human tissue; treatment response; aged; unclassified drug; human cell; major clinical study; janus kinase 2; bone metastasis; adjuvant therapy; cancer patient; lymph node metastasis; cancer incidence; tumor associated leukocyte; biological marker; cancer immunotherapy; gene amplification; epidermal growth factor receptor 2; cohort analysis; gene frequency; cancer screening; brca1 protein; medical record review; retrospective study; protein p53; axillary lymph node; fluorescence in situ hybridization; microsatellite instability; myc protein; breast carcinoma; tumor protein; atm protein; gene loss; cyclin dependent kinase inhibitor 2a; neoadjuvant chemotherapy; estrogen receptor; progesterone receptor; hla a antigen; stroma cell; genetic screening; protein msh6; eribulin; olaparib; programmed death 1 ligand 1; notch4 receptor; transcription factor runx1; copy number variation; molecular diagnosis; triple negative breast cancer; janus kinase 2 inhibitor; germline mutation; next generation sequencing; sapacitabine; disease burden; human; female; article; pembrolizumab; programmed death 1 ligand 2; rad21 protein; atezolizumab; pik3ca protein; ercc5 protein; nfkbia protein; protein mga; spen protein; tceb1 protein
Journal Title: Journal of Molecular Diagnostics
Volume: 21
Issue: 2
ISSN: 1525-1578
Publisher: Elsevier Science, Inc.  
Date Published: 2019-03-01
Start Page: 307
End Page: 317
Language: English
DOI: 10.1016/j.jmoldx.2018.10.006
PUBMED: 30576871
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 April 2019 -- Source: Scopus
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MSK Authors
  1. Khedoudja Nafa
    184 Nafa
  2. Marc Ladanyi
    870 Ladanyi
  3. David Hyman
    187 Hyman
  4. Ahmet Zehir
    153 Zehir
  5. Michael Forman Berger
    386 Berger
  6. Maria Eugenia Arcila
    343 Arcila
  7. Dara Stacy Ross
    43 Ross
  8. Jose T Baselga
    404 Baselga
  9. Pedram Razavi
    25 Razavi
  10. Rym Benayed
    72 Benayed
  11. Jason Chih-Peng Chang
    14 Chang
  12. Paolo Cotzia
    13 Cotzia
  13. Sounak Gupta
    6 Gupta