The following is a summary of “Germline mutational landscape of genitourinary cancers and its indication for prognosis and risk” published in the November 2022 issue of Urology by Yang et al.


Germline mutations are a major cause of cancers that run in families. Most of what researchers know about germline mutations in genitourinary cancer is that they don’t know what they look like or how they affect a patient’s prognosis. The Cancer Genome Atlas (TCGA) was used to get variant and relevant clinical data on 10,389 cancer patients. In addition, filtering was done on 206 genitourinary cancer patients’ data that had information about germline mutations. This included patients with bladder urothelial carcinoma (BLCA), kidney chromophobe carcinoma (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and prostate adenocarcinoma (PRAD). Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), variants were categorized into 3 groups: pathogenic, likely pathogenic, and not pathogenic. Risk analysis was helped by the Genome Aggregation Database (gnomAD) database.

In that order, germline mutations were found in 48, 7, 44, 45, and 62 patients in BLCA, KICH, KIRC, KIRP, and PRAD. There were found to be pathogenic germline mutations in 26 genes and likely pathogenic mutations in 33 genes. The top mutations for kidney cancer were GJB2, MET, MUTYH, and VHL. The top mutations for bladder cancer were ATM and CHEK2, and the top mutations for prostate cancer were ATM and BRCA1. Most mutations were of the frameshift, stop gained, and missense types. The number of stop-gain mutations in BLCA was the highest (22/48, or 45.8%). For all types of cancer, there was no difference in age between patients in the pathogenic, likely pathogenic, and non-pathogenic groups. No matter whether PRAD was included (P=0) or not (P<0.001), far more men than women were overweight. For all genitourinary cancers, the overall survival rate of people with pathogenic or likely pathogenic germline mutations was much lower than that of the non-pathogenic group.

More importantly, analyses helped by the gnomAD database showed that pathogenic or likely pathogenic germline mutations significantly increased the risk of genitourinary cancer in the population, with odds ratios of 14.88 (95% CI: 11.80–18.77) and 33.18 (95% CI: 24.90–44.20), respectively. The status of germline mutations in genitourinary cancers has been completely mapped out. Pathogenic and likely pathogenic germline mutations made genitourinary cancers more likely and gave a bad outlook.

Source: bmcurol.biomedcentral.com/articles/10.1186/s12894-022-01141-1