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

58 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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