Clinical and genetic characteristics in pancreatic cancer from Chinese patients revealed by whole exome sequencing

作者：Yonggang He, Wen Huang, Yichen Tang, Yuming Li, Xuehui Peng, Jing Li, Jing Wu, Nan You, Ling Li, Chuang Liu, Lu Zheng, Xiaobing Huang · 发表于：Frontiers in Oncology · 年份：2023 · DOI：10.3389/fonc.2023.1167144 · 被引用次数：9 · 研究领域：Pancreatic and Hepatic Oncology Research、Cancer Genomics and Diagnostics、Renal cell carcinoma treatment

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide, mostly as a result of the absence of early detection and specific treatment solutions. Consequently, identifying mutational profiles and molecular biomarkers is essential for increasing the viability of precision therapy for pancreatic cancer. Methods We collected blood and tumor 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 PDAC 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 individuals examined for programmed cell death ligand 1(PD-L1) expression, 15 (36.6%) had...