AUTHOR=He Yonggang , Huang Wen , Tang Yichen , Li Yuming , Peng Xuehui , Li Jing , Wu Jing , You Nan , Li Ling , Liu Chuang , Zheng Lu , Huang Xiaobing 

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

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1167144

DOI=10.3389/fonc.2023.1167144

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>We collected blood and tumor tissue samples from 47 Chinese pancreatic cancer patients and used whole-exome sequencing (WES) to evaluate the genetic landscape.</p></sec><sec><title>Results</title><p>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&gt;T/p. R1618*, WRN c.1105C&gt;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%, <italic>p</italic> = 0.01), GAS6(6.4% vs. 0.5%, <italic>p</italic> = 0.035), MMP17(6.4% vs. 0.5%, <italic>p</italic> = 0.035), ITM2B (6.4% vs. 0.5%, <italic>p</italic> = 0.035) and USP7 (6.4% vs. 0.5%, <italic>p</italic>= 0.035) as well as a reduced mutation frequency of SMAD4 (17.0% vs. 31.5%, <italic>p</italic> = 0.075) and CDKN2A (12.8% vs. 47.3%, <italic>p</italic> &lt; 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 positive PD-L1 expression. The median tumor mutational burden (TMB) was found to be 12muts (range, 0124). The TMB index was higher in patients with mutant-type KRAS MUT/TP53 MUT (<italic>p</italic> &lt; 0.001), CDKN2A (<italic>p</italic> = 0.547), or SMAD4 (<italic>p</italic> = 0.064) compared to patients with wild-type KRAS/TP53, CDKN2A, or SMAD4.</p></sec><sec><title>Conclusions</title><p>We exhibited real-world genetic traits and new alterations in Chinese individuals with cancer of the pancreas, which might have interesting implications for future individualized therapy and medication development.</p></sec>