Genomic Alterations and Possible Druggable Mutations in Carcinoma of Unknown Primary (CUP)

Abstract

SummaryCarcinoma of Unknown Primary (CUP) is a heterogeneous and metastatic disease where the primary site of origin is undetectable. Currently, chemotherapy is an only state-of-art treatment option for the CUP patient. Employing molecular profiling of the tumour, particularly mutation detection, offers a new treatment for CUP in a personalized fashion. Here, we analyzed mutation and copy number alterations profile of 1,709 CUP samples deposited in GENIE cohort and explored potential druggable mutations. We identified 52 significant mutated genes (SMG) among CUP samples, of which 13 (25%) of SMG were potentially targetable with drugs reproved for the know primary tumour or undergoing clinical trials. The most variants detected were TP53 (43%), KRAS (19.90%), KMT2D (12.60%), and CDKN2A (10.30%). Additionally, the presence of similar variants of TERT promoter in CUP compared to NSCLC samples suggests these mutations may serve as a diagnostic marker for identifying the primary tumour in CUP. Taken together, analyzing mutation profiling of the CUP tumours may open a new way of identifying druggable targets and consequently administrating appropriate treatment in a personalized manner.