IBCN 2018: HRAS Mutations in Early-Onset Bladder Cancer

Rotterdam, The Netherlands (UroToday.com) Robert Stöhrv discussed his research on HRAS mutations and bladder cancer. Bladder tumors of early-onset patients are rare and seem to exhibit unique features, both clinically and pathologically. The few available molecular studies observing a low frequency of the known alterations found in bladder cancer lead to the hypothesis of a different mutational profile between the various age groups.

Recently, a study of few samples of young patients reported a higher percentage of HRAS mutations among the early-onset cohort compared to elderly samples. Due to the low sample size, the impact of these alterations of the age of onset and the frequency among young patients remain unclear and need further investigation.

The aim this study was to test the distribution of HRAS mutations among the largest cohort of early-onset cases to date and to compare them with a consecutive group of bladder tumors. 141 early-onset patients aged 45 years old or younger and 144 consecutive samples were used for comparison. After microdissection, isolation of DNA and amplification the five established hotspot regions of the HRAS gene were examined by using SNaPshot approach. Chi-squared and Fisher´s exact test were appropriately used for comparison between the two cohorts. Kruskal-Wallis non-parametric test was also calculated.

A significantly higher number of HRAS mutations was found in tumors from the early onset cohort compared to the consecutive samples (15.6% vs. 5.6%, p=0.01). After stratifying the young samples according to the mutational HRAS status, we observed a significantly younger median age among the early-onset mutation carrier than for not mutated patients, with 32 and 40 years (p=0.01), respectively. This difference was not found among the consecutive cohort.

They concluded that tumors of young patients showed a significantly higher frequency of HRAS mutations compared to the consecutive cohort. Thus, the tested mutations might play a more important role for the development of bladder cancer especially among the youngest cohort of early-onset patients. These findings strengthen the idea of a different molecular scenario between consecutive and early-onset bladder cancer tumors.

Presented by: Robert Stöhr, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, German

Written by: Stephen B. Williams, M.D., Associate Professor, Division of Urology, The University of Texas Medical Branch, Galveston, TX. and Ashish M. Kamat, M.D. Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX at the 16th Annual Meeting of the International Bladder Cancer Network (IBCN) October 11-13, 2018 - the Inntel Hotels Rotterdam Centre, Rotterdam, The Netherlands