Semantic Scholar Open Access 2025 4 sitasi

Pathogenic germline variants in Chinese pancreatic adenocarcinoma patients

Xiaoyi Yin Hui Shen Huan Wang Qingchen Wang Shan Zhang +34 lainnya

Lihat Sumber DOI

Abstrak

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. The prevalence of mutations that can predispose to pancreatic adenocarcinoma (PDAC) remains unclear, especially in underrepresented populations. Here, the authors create a germline mutation map of 1,123 Chinese PDAC patients and compare them to cohorts from other populations, finding CFTR as a potential driver.

Topik & Kata Kunci

Medicine

Penulis (39)

Xiaoyi 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

Guo-xiao Zhang

Yikai Li

Penghao Li

W. Jing

Bin Song

Kai-lian Zheng

Gang Li

Yijie Zhang

Hui Jiang

Cong Wu

Zhijian Song

Gang Niu

Qiangzu Zhang

Jian-You Guo

Zhen Sun

Fengxian Han

Yunguang Li

Dong Gao

Haojie Jin

Hongbo Yang

Jing Li

Gang Jin

Format Sitasi

APA MLA BibTeX

Yin, X., Shen, H., Wang, H., Wang, Q., Zhang, S., Zhang, C. et al. (2025). Pathogenic germline variants in Chinese pancreatic adenocarcinoma patients. https://doi.org/10.1038/s41467-025-57520-3

Akses Cepat

Lihat di Sumber doi.org/10.1038/s41467-025-57520-3

Informasi Jurnal

Tahun Terbit: 2025
Bahasa: en
Total Sitasi: 4×
Sumber Database: Semantic Scholar
DOI: 10.1038/s41467-025-57520-3
Akses: Open Access ✓