Comprehensive genomic landscape in pancreatic cancer using whole-exome sequencing

e16307 Background: Pancreatic ductal adenocarcinoma is one of the fatal malignancies in the world, mostly as a result of the absence of early detection and specific treatment solutions. Consequently, identifying mutational profiles and molecular biomarker are essential for increasing the viability of precision therapy for pancreatic cancer. Methods: We gathered blood and tumour tissue samples from 47 Chinese pancreatic cancer patients and used whole-exome sequencing (WES) to evaluate the genetic landscape. Results: Our results showed the most frequently somatic alteration genes were KRAS (74.5%), TP53 (51.1%), SMAD4 (17%), ARID1A (12.8%), CDKN2A (12.8%), TENM4 (10.6%), TTN (8.5%), RNF43 (8.5%), FLG (8.5%) and GAS6 (6.4%) in Chinese pancreatic ductal adenocarcinoma patients. We also found that three deleterious germline mutations ( ATM c.4852C > T/p. R1618*, WRN c.1105C > T/p. R369*, PALB2 c.2760dupA/p. Q921Tfs*7) and two novel fusions ( BRCA1-RPRML, MIR943 (intergenic)- FGFR3). When compared to the Cancer Genome Atlas (TCGA) database, there is a greater mutation frequency of TENM4 (10.6% vs. 1.6%, p= 0.01), GAS6 (6.4% vs. 0.5%, p= 0.035), MMP17 (6.4% vs. 0.5%, p= 0.035), ITM2B (6.4% vs. 0.5%, p= 0.035) and USP7 (6.4% vs. 0.5%, p= 0.035) as well as a reduced mutation frequency of SMAD4 (17.0% vs. 31.5%, p= 0.075) and CDKN2A (12.8% vs. 47.3%, p< 0.001) were observed in the Chinese cohort. Among the 41 individual examined for PD-L1 expression, 15 (36.6%) had positive PD-L1 expression. The median tumour mutational burden (TMB) was found to be 12 muts (range, 0-124). The TMB index was higher in patients with mutant-type KRAS MUT/ TP53 MUT ( p< 0.001), CDKN2A ( p= 0.547), or SMAD4 ( p= 0.064) compared to patients with wild-type KRAS/ TP53, CDKN2A, or SMAD4. Conclusions: We exhibited real-world genetic traits and new alterations in Chinese individuals with cancer of pancreas, which might have interesting implications for future individualized therapy and medication development.