The germline mutational landscape of genitourinary cancers and its indication for prognosis and risk

作者：Yong Yang, Guoying Zhang, Chen Hu, Wei Luo, Haiyang Jiang, Shaoyou Liu, Hong Yang · 发表于：BMC Urology · 年份：2022 · DOI：10.1186/s12894-022-01141-1 · 被引用次数：11 · 研究领域：Bladder and Urothelial Cancer Treatments、Cancer Genomics and Diagnostics、Renal cell carcinoma treatment

BACKGROUND: Germline mutations represent a high risk of hereditary cancers in population. The landscape and characteristics of germline mutations in genitourinary cancer are largely unknown, and their correlation with patient prognosis has not been defined. METHODS: Variant data and relevant clinical data of 10,389 cancer patients in The Cancer Genome Atlas (TCGA) database was downloaded. The subset of data of 206 genitourinary cancer patients containing bladder urothelial carcinoma (BLCA), kidney chromophobe carcinoma (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP) and prostate adenocarcinoma (PRAD) cancer with germline mutation information was filtered for further analysis. Variants were classified into pathogenic, likely pathogenic and non-pathogenic categories based on American College of Medical Genetics and Genomics (ACMG) guidelines. Genome Aggregation Database (gnomAD) database was used to assist risk analysis. RESULTS: There were 48, 7, 44, 45 and 62 patients with germline mutations identified in BLCA, KICH, KIRC, KIRP and PRAD, respectively. Pathogenic germline mutations from 26 genes and likely pathogenic mutations from 33 genes were revealed. GJB2, MET, MUTYH and VHL mutations ranked top in kidney cancers, and ATM and CHEK2 mutations ranked top for bladder cancer, while ATM and BRCA1 mutations ranked top for prostate cancer. Frameshift, stop gained and missense mutations were the predominant mutation types. BLCA exhib...