Enrichment of FGFR3-TACC3 Fusions in Patients With Bladder Cancer Who Are Young, Asian, or Have Never Smoked.

PURPOSE

(fibroblast growth factor receptor 3-transforming acidic coiled coil-containing protein 3) fusions have recently been identified as driver mutations that lead to the activation of in bladder cancer and other tumor types and are associated with sensitivity to tyrosine kinase inhibitors. We examined the clinical and molecular characteristics of patients with fusions and hypothesized that they are enriched in a subset of patients with bladder cancer.

MATERIALS AND METHODS

We correlated somatic fusions with clinical and molecular features in two cohorts of patients with bladder cancer. The first cohort consisted of the muscle-invasive bladder cancer (MIBC) data set (n = 412) from The Cancer Genome Atlas. The second cohort consisted of patients with MIBC or high-grade non-MIBC at the Dana-Farber Cancer Institute that had targeted capture sequencing of a selected panel of cancer genes (n = 356). All statistical tests were two sided. The clinical response of one patient with bladder cancer to an FGFR3 inhibitor was investigated.

RESULTS

Overall, 751 patients with high-grade bladder cancer without fusions and 17 with fusions were identified in the pooled analysis of the data sets from The Cancer Genome Atlas and the Dana-Farber Cancer Institute. fusions were enriched in patients age ≤ 50 years versus age 51 to 65 years versus those older than 65 years (pooled, = .002), and were observed in four (12%) of 33 patients age ≤ 50 years in the pooled analysis. Similarly, fusions were significantly more common in Asians (13%) compared with African Americans (4%) and whites (2%; pooled, < .001), as well as in never smokers (5.6%) compared with ever smokers (1.1%; pooled, < .001). One patient with the fusion who was treated with an FGFR3 inhibitor achieved complete remission for 10 months.

CONCLUSION

Clinical testing to identify fusions should be prioritized for patients with bladder cancer who are younger, never smokers, and/or Asian.