Abstract 2652: Pan-cancer analysis of programmed death-ligand 1 (PD-L1) amplifications

Abstract

Abstract PD-L1, located in the chromosomal region 9p28, is a ligand of programmed cell death protein 1 (PD-1) and has been described as immune checkpoint regulator that allows cancers to evade the host immune system. To stratify patients for treatment with PD-1 inhibitors, PD-L1 expression is currently intensively studied on RNA and protein levels. However, no comprehensive study of PD-L1 amplifications including many cancer types has been performed so far. We investigated PD-L1 amplifications in eighteen cancer types that were copy number profiled, gene expression profiled and clinically characterized by the TCGA consortium: Acute Myeloid Leukemia (LAML), Bladder Urothelial Carcinoma (BLCA), Brain Lower Grade Glioma (LGG), Breast invasive carcinoma (BRCA), Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), Colorectal adenocarcinoma (COADREAD), Glioblastoma multiforme (GBM), Head and Neck squamous cell carcinoma (HNSC), Kidney renal clear cell carcinoma (KIRC), Liver hepatocellular carcinoma (LIHC), Lung adenocarcinoma (LUAD), Lung squamous cell carcinoma (LUSC), Ovarian serous cystadenocarcinoma (OV), pancreatic adenocarcinoma (PAAD), Sarcoma (SARC), Skin Cutaneous Melanoma (SKCM), Stomach adenocarcinoma (STAD) and Uterine Corpus Endometrial Carcinoma (UCEC). We found a diverse landscape of focal PD-L1 amplification, 9p chromosome arm amplifications and polysomy 9. Focal amplifications had the highest incidence in OV (10.7%), LUSC (9.8%), HNSC (8.6%), BLCA (8.3%), SARC (8.2%), CESC (7.1%), STAD (6.8%) and BRCA (5.3%). 9p amplifications were most frequently found in OV (12.6%), BLCA (7.4%), BRCA (6.8%) and LUAD (5.2%). Polysomy 9 had the highest incidence in COADREAD (14.0%), HNSC (13.6%), CESC (11.2%), SARC (9.4%) and STAD (7.2%), BLCA (5.9%) and GBM (5.5%). In a pooled analysis of focal and non-focal alterations, PD-L1 amplifications positively correlated with gene expression in nine cancer types and significantly (p < 0.05) shortened overall survival in five cancer types. In summary, PD-L1 amplifications represent a frequent genetic alteration that occurs in many cancer types and could potentially be exploited for patient stratification and immune therapy. Citation Format: Jan Budczies, Michael Bockmayr, Frederick Klauschen, Wilko Weichert, Carsten Denkert, Albrecht Stenzinger. Pan-cancer analysis of programmed death-ligand 1 (PD-L1) amplifications. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2652.