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We used DNA content flow cytometry followed by oligonucleotide array based comparative genomic hybridization to survey the genomes of 326 tumors, including 41 untreated surgically resected triple negative breast cancers (TNBC). A high level (log2ratio ≥1) 9p24 amplicon was found

We used DNA content flow cytometry followed by oligonucleotide array based comparative genomic hybridization to survey the genomes of 326 tumors, including 41 untreated surgically resected triple negative breast cancers (TNBC). A high level (log2ratio ≥1) 9p24 amplicon was found in TNBC (12/41), glioblastomas (2/44), and colon carcinomas (2/68). The shortest region of overlap for the amplicon targets 9p24.1 and includes the loci for PD-L1, PD-L2, and JAK2 (PDJ amplicon). In contrast this amplicon was absent in ER+ (0/8) and HER2+ (0/15) breast tumors, and in pancreatic ductal adenocarcinomas (0/150). The PDJ amplicon in TNBCs was correlated with clinical outcomes in group comparisons by two-sample t-tests for continuous variables and chi-squared tests for categorical variables. TNBC patients with the PDJ amplicon had a worse outcome with worse disease-free and overall survival. Quantitative RT-PCR confirmed that the PDJ amplicon in TNBC is associated with elevated expression of JAK2 and of the PD-1 ligands. These initial findings demonstrate that the PDJ amplicon is enriched in TNBC, targets signaling pathways that activate the PD-1 mediated immune checkpoint, and identifies patients with a poor prognosis.

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    Title
    • Genomic Amplification of 9p24.1 Targeting JAK2, PD-L1, and PD-L2 is Enriched in High-Risk Triple Negative Breast Cancer
    Date Created
    2015-07-03
    Resource Type
  • Text
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    Identifier
    • Digital object identifier: 10.18632/oncotarget.4494
    • Identifier Type
      International standard serial number
      Identifier Value
      1949-2553
    Note
    • The final version of this article, as published in Oncotarget, can be viewed online at: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5b%5d=4494

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    Barrett, M. T., Anderson, K. S., Lenkiewicz, E., Andreozzi, M., Cunliffe, H. E., Klassen, C. L., . . . Pockaj, B. A. (2015). Genomic amplification of 9p24.1 targetingJAK2, PD-L1,andPD-L2is enriched in high-risk triple negative breast cancer. Oncotarget, 6(28), 26483-26493. doi:10.18632/oncotarget.4494

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