Genetic subtypes of bladder cancer reflect breast cancer biology

A comprehensive genetic analysis of invasive bladder cancer tumors has found that the disease shares genetic similarities with two forms of breast cancer, according to researchers at the University of North Carolina Lineberger Cancer Center. Bladder cancer, which is the fourth most common malignancy in men and ninth most common in women in the United States, claimed more than 15,000 patients last year.

The analysis of 262 bladder cancer tumors, published online by the Proceedings of the National Academy of Sciences, reveals that the invasive form of the disease can be classified into two distinct genetic subtypes – basal-like and luminal – which were shown to be highly similar to the basal and luminal subtypes of breast cancer first described by Charles Perou, PhD, May Goldman Shaw Distinguished Professor of Molecular Oncology at UNC Lineberger. A greater understanding of the genetic basis of cancers such as breast cancer has led to the development of new therapies and diagnostic aids.

“It will be particularly interesting to see whether the bladder subtypes, like the breast subtypes, are useful in stratification for therapy,” said lead author William Kim, MD, associate professor with the UNC School of Medicine.

The mapping of the genetic signaling pathways of the breast cancer subtypes has led to development of drugs and diagnostic aids that aid physicians in determining the best course of therapy for patients with that disease. As the identified bladder cancer subtypes share many of the same genetic signaling pathways of breast cancer, researchers hope that the identification of the genetic subtypes can lead to similar advances.

“Currently there are no approved targeted therapies for bladder cancer. Our hope is that the identification of these subtypes will aid in the discovery of targetable pathways that will advance bladder cancer treatment,” said lead author Jeffrey Damrauer, graduate student in the Curriculum of Genetics and Molecular Biology.

The study also revealed a possible answer to why women diagnosed with bladder cancer have overall poorer outcomes compared to males. Analysis from female patients showed a significantly higher incidence of the deadlier, basal-like tumors, but researchers said that more research is needed before a definite link between the subtype and survival can be confirmed.

Dr. Kim’s lab has developed a gene map, BASE47, that proved successful as a prognostic aid when applied to the tumor samples in the study. The PAM50 genetic test, a similar genetic map developed in the Perou lab, was recently approved as a clinical diagnostic tool by the FDA.

Additional LCCC members contributing to this work are Katherine Hoadley, PhD; David Chism, MD; Cheng Fan; Christopher Tiganelli, MD; Sara Wobker, MD; Jen Jen Yeh, MD; Matthew Milowsky, MD; and Joel Parker, PhD. This work was supported by National Institutes of Health Grant R01 CA142794 and Integrative Vascular Biology Training Grant T32-HL069768. Dr. Kim is a Damon Runyon Merck Clinical Investigator. Dr. Kim and Damrauer are inventors on the patent for the BASE47.