title: Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer.
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.
authors: Department of Research, Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
authors: Michael T
authors: MT
authors: Barrett
authors: Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors: Karen S
authors: KS
authors: Anderson
authors: Department of Research, Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
authors: Elizabeth
authors: E
authors: Lenkiewicz
authors: Department of Research, Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
authors: Mariacarla
authors: M
authors: Andreozzi
authors: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors: Heather E
authors: HE
authors: Cunliffe
authors: Division of General Surgery, Section of Surgical Oncology, Mayo Clinic in Arizona, Phoenix, Arizona, United States of America.
authors: Christine L
authors: CL
authors: Klassen
authors: Section of Biostatistics, Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
authors: Amylou C
authors: AC
authors: Dueck
authors: Department of Pathology and Laboratory Medicine, Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
authors: Ann E
authors: AE
authors: McCullough
authors: Vanderbilt University, Nashville, Tennessee, United States of America.
authors: Srikanth K
authors: SK
authors: Reddy
authors: Division of Hematology-Oncology, Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
authors: Ramesh K
authors: RK
authors: Ramanathan
authors: Division of Hematology-Oncology, Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
authors: Donald W
authors: DW
authors: Northfelt
authors: Division of General Surgery, Section of Surgical Oncology, Mayo Clinic in Arizona, Phoenix, Arizona, United States of America.
authors: Barbara A
authors: BA
authors: Pockaj
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics; D002899:Chromosomes, Human, Pair 9; D015179:Colorectal Neoplasms / Q000235:genetics; D055028:Comparative Genomic Hybridization; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005909:Glioblastoma / Q000235:genetics; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics; D010641:Phenotype; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015854:Up-Regulation
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: 9p24.1 amplicon; JAK2; PD-L1; flow sorting; triple negative breast cancer