Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer

Michael T. Barrett, Karen Anderson, Elizabeth Lenkiewicz, Mariacarla Andreozzi, Heather E. Cunliffe, Christine L. Klassen, Amylou C. Dueck, Ann E. McCullough, Srikanth K. Reddy, Ramesh K. Ramanathan, Donald W. Northfelt, Barbara A. Pockaj

    Research output: Contribution to journalArticle

    50 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)26483-26493
    Number of pages11
    JournalOncotarget
    Volume6
    Issue number28
    DOIs
    StatePublished - 2015

    Fingerprint

    Triple Negative Breast Neoplasms
    Comparative Genomic Hybridization
    Glioblastoma
    Oligonucleotide Array Sequence Analysis
    Disease-Free Survival
    Flow Cytometry
    Colon
    Adenocarcinoma
    Genome
    Breast Neoplasms
    Ligands
    Carcinoma
    Polymerase Chain Reaction
    DNA
    Neoplasms

    Keywords

    • 9p24.1 amplicon
    • Flow sorting
    • JAK2
    • PD-L1
    • Triple negative breast cancer

    ASJC Scopus subject areas

    • Oncology

    Cite this

    Barrett, M. T., Anderson, K., Lenkiewicz, E., Andreozzi, M., Cunliffe, H. E., Klassen, C. L., ... Pockaj, B. A. (2015). Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer. Oncotarget, 6(28), 26483-26493. https://doi.org/10.18632/oncotarget.4494

    Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer. / Barrett, Michael T.; Anderson, Karen; Lenkiewicz, Elizabeth; Andreozzi, Mariacarla; Cunliffe, Heather E.; Klassen, Christine L.; Dueck, Amylou C.; McCullough, Ann E.; Reddy, Srikanth K.; Ramanathan, Ramesh K.; Northfelt, Donald W.; Pockaj, Barbara A.

    In: Oncotarget, Vol. 6, No. 28, 2015, p. 26483-26493.

    Research output: Contribution to journalArticle

    Barrett, MT, Anderson, K, Lenkiewicz, E, Andreozzi, M, Cunliffe, HE, Klassen, CL, Dueck, AC, McCullough, AE, Reddy, SK, Ramanathan, RK, Northfelt, DW & Pockaj, BA 2015, 'Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer' Oncotarget, vol. 6, no. 28, pp. 26483-26493. https://doi.org/10.18632/oncotarget.4494
    Barrett, Michael T. ; Anderson, Karen ; Lenkiewicz, Elizabeth ; Andreozzi, Mariacarla ; Cunliffe, Heather E. ; Klassen, Christine L. ; Dueck, Amylou C. ; McCullough, Ann E. ; Reddy, Srikanth K. ; Ramanathan, Ramesh K. ; Northfelt, Donald W. ; Pockaj, Barbara A. / Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer. In: Oncotarget. 2015 ; Vol. 6, No. 28. pp. 26483-26493.
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