Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology

JS Damrauer, KA Hoadley, DD Chism… - Proceedings of the …, 2014 - National Acad Sciences
JS Damrauer, KA Hoadley, DD Chism, C Fan, CJ Tiganelli, SE Wobker, JJ Yeh, MI Milowsky…
Proceedings of the national academy of sciences, 2014National Acad Sciences
We sought to define whether there are intrinsic molecular subtypes of high-grade bladder
cancer. Consensus clustering performed on gene expression data from a meta-dataset of
high-grade, muscle-invasive bladder tumors identified two intrinsic, molecular subsets of
high-grade bladder cancer, termed “luminal” and “basal-like,” which have characteristics of
different stages of urothelial differentiation, reflect the luminal and basal-like molecular
subtypes of breast cancer, and have clinically meaningful differences in outcome. A gene set …
We sought to define whether there are intrinsic molecular subtypes of high-grade bladder cancer. Consensus clustering performed on gene expression data from a meta-dataset of high-grade, muscle-invasive bladder tumors identified two intrinsic, molecular subsets of high-grade bladder cancer, termed “luminal” and “basal-like,” which have characteristics of different stages of urothelial differentiation, reflect the luminal and basal-like molecular subtypes of breast cancer, and have clinically meaningful differences in outcome. A gene set predictor, bladder cancer analysis of subtypes by gene expression (BASE47) was defined by prediction analysis of microarrays (PAM) and accurately classifies the subtypes. Our data demonstrate that there are at least two molecularly and clinically distinct subtypes of high-grade bladder cancer and validate the BASE47 as a subtype predictor. Future studies exploring the predictive value of the BASE47 subtypes for standard of care bladder cancer therapies, as well as novel subtype-specific therapies, will be of interest.
National Acad Sciences