BASE47 gene set predictor as an identifier of 'basal-like' subtype of urothelial carcinoma of the bladder in African Americans

300 Background: African-Americans [AAs] have a higher cancer-specific mortality when compared to whites with urothelial carcinoma (UC) of the bladder. Recent gene expression studies identified two intrinsic, molecular subsets of high-grade bladder cancer: “luminal” and “basal-like”, which can be accurately classified using the BASE47 gene set predictor. We applied the BASE47 gene set predictor to AA tumors and assessed enrichment for basal-like bladder tumors. Methods: Gene expression data from 179 high-grade, muscle invasive bladder tumors—9 AAs and 170 non-AAs (whites, Asians, and race not defined) from the TCGA was analyzed. Prediction analysis of microarrays (PAM) was used to derive the Bladder cancer Analysis of Subtypes by Expression (BASE47) gene set predictor and validated with 2 independent datasets. Comparisons of gene expressions patterns between bladder and breast intrinsic subtypes were peformed. Results: The BASE47 subtype classifier was highly concordant with Consensus Cluster subtype calls on 2 independent datasets. Based on the BASE47 gene classifier, a significant fraction of the tumors from AA (7/9) were classified as “basal-like” (P=0.07 Two tail). Basal-like bladder tumors trended strongly towards a worse prognosis (P=0.09 TCGA, 0.0194 MSKCC). Gene expressions patterns for“basal-like” and luminal bladder cancer correlated highly with basal-like breast and luminal A/B subtypes respectively. In addition, a subset of “basal-like” bladder cancer was found to be a claudin-low subtype. Conclusions: We have identified two molecular subtypes of high-grade bladder cancer that highly reflect the intrinsic subtypes of breast cancer. The BASE47 is a robust subtype classifier that can reliably distinguish basal and luminal bladder cancers. African-Americans have enrichment in the “basal-like” subtype of bladder cancer. These results will be validated in an independent set of samples as well as on FFPE tumors.