 Pathogenic germline variants in Chinese pancreatic adenocarcinoma patientsXiaoyi Yin,
Hui Shen,
Huan Wang,
Qingchen Wang,
Shan Zhang,
Chunming Zhang,
Qi Jia,
Shiwei Guo,
Xiongfei Xu,
Wenhui Zhang,
Bo Li,
Xiaohan Shi,
Suizhi Gao,
Meilong Shi,
Xuenan Zhao,
Sheng Wang,
Jiawei Han,
Guoxiao Zhang,
Yikai Li,
Penghao Li,
Wei Jing,
Bin Song,
Kailian Zheng,
Gang Li,
Yijie Zhang,
Hui Jiang,
Cong Wu,
Zhijian Song,
Gang Niu,
Qiangzu Zhang,
Jianglong Guo,
Zhen Sun,
Fengxian Han,
Yunguang Li,
Dong Gao,
Haojie Jin (),
Hongbo Yang (),
Jing Li () and
Gang Jin ()
Nature Communications, 2025, vol. 16, issue 1, 1-20 Abstract: Abstract Putting pancreatic adenocarcinoma (PAAD) screening into perspective for high-risk individuals could significantly reduce cancer morbidity and mortality. Previous studies have profiled somatic mutations in PAAD. In contrast, the prevalence of mutations in PAAD predisposition genes has not been defined, especially in the Asian population. Using a multi-tier cohort design and whole genome/exome sequencing, we create a comprehensive germline mutation map of PAAD in 1,123 Chinese cancer patients in comparison with 11 pan-ethnic studies. For well-known pathogenic/likely pathogenic germline variants, Chinese patients exhibit overlapping but distinct germline mutation patterns comparing with Western cohorts, highlighted by lower mutation rates in known PAAD genes including BRCA1, BRCA2, ATM, CDKN2A, and CHEK2, and distinct mutations in CFTR, RAD51D, FANCA, ERCC2, and GNAS exclusive to Chinese patients. CFTR emerges as a top candidate gene following loss of heterozygosity analysis. Using an integrative multi-omics and functional validation paradigm, we discover that deleterious variants of uncertain significance may compromise CFTR’s tumor suppressor function, and demonstrate the clinical relevance by using patient derived organoids for drug screen. Our multifaceted approach not only deepens the knowledge of population differences in PAAD germline mutations but also unveils potential avenues for targeted therapeutic interventions. Date: 2025 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57520-3 Ordering information: This journal article can be ordered from DOI: 10.1038/s41467-025-57520-3 Access Statistics for this article Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie More articles in Nature Communications from Nature |
Is your work missing from RePEc? Here is how to contribute.
Questions or problems? Check the EconPapers FAQ or send mail to .
EconPapers is hosted by the
School of Business at Örebro University.