Main driver genes and BRCA mutation in Chinese patients with pancreatic adenocarcinoma.

Abstract

e15741 Background: Data on pathogenic genetic alterations in Chinese patients with pancreatic adenocarcinoma (PAC) are limited. Especially, as BRCA mutations may become potential biomarkers guiding therapy for PAC patients, the prevalence of BRCA mutations in Chinese patients remains largely unknown.We performed the study to analyze genes mutational landscape and determine the prevalence of BRCA mutations in Chinese PAC patients. Methods: We reviewed clinical characteristics and genes mutations of 134 patients with a pathologically confirmed PAC from West China Hospital of Sichuan University between May 2016 and November 2018. All of them underwent gene-testing and genes variant evaluation with a panel of 381 genes by next-generation sequencing (NGS). The test samples were mainly from primary pancreatic lesions, other were from peripheral blood and metastatic sites. All main driver gene mutations and clinical stages were measured to determine associations of driver gene mutations, the number of altered genes, the level of CA199 with clinical stage. Results: Of the 134 patients, 73 (54.5%) were men with a median age of 58 (range from 34 to 82) years. The major driver mutations were KRAS (89.6%), TP53 (71.6%), CDKN2A (26.9%), SMAD4 (18.7%) and ARID1A (10.4%). The majority of patients (76.9%) had 2 genes or more genes mutations, KRAS/TP53 and KRAS/TP53/CDKN2A were the most frequently combinate types. Stages of PAC was relevant to numbers of altered genes (p = 0.040) and the level of CA199 (p = 0.002). Five (3.7%) patients with BRCA mutations were identified, two patients had somatic BRCA2 variants, one patient had somatic BRCA1 mutation and the other two patients had germline BRCA2 mutation. Two patients with germline BRCA2 mutations received olaparib and keep stable disease for 4 months and more than 8 months. Our finding revealed patients with PAC had a low TMB (median 3.81 per Mb (range 0.81-9 per Mb)) and PD-L1 expression (16/36, 44.4%), nearly all of them were MSS (50/51,98.0%), just three patients with dMMR (3/134,2.2%). Conclusions: The PAC patient commonly harbored two or more number of five major driver mutations including KRAS, TP53, CDKN2A, SMAD4 and ARID1A. The frequency of BRCA1/2 mutations in Chinese patients with PAC was 3.7%. Olaparib may be effective for PAC patients with BRCA mutations. The PAC may be poor response to immunotherapy.