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.
Details
- Genomic Amplification of 9p24.1 Targeting JAK2, PD-L1, and PD-L2 is Enriched in High-Risk Triple Negative Breast Cancer
- Barrett, Michael T. (Author)
- Anderson, Karen (Author)
- Lenkiewicz, Elizabeth (Author)
- Andreozzi, Mariacarla (Author)
- Cunliffe, Heather E. (Author)
- Klassen, Christine L. (Author)
- Dueck, Amylou C. (Author)
- McCullough, Ann E. (Author)
- Reddy, Srikanth K. (Author)
- Ramanathan, Ramesh K. (Author)
- Northfelt, Donald W. (Author)
- Pockaj, Barbara A. (Author)
- Biodesign Institute (Contributor)
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Digital object identifier: 10.18632/oncotarget.4494
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Identifier TypeInternational standard serial numberIdentifier Value1949-2553
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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