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Genomics of Bladder Cancer Remain Largely Unknown

Angelica Welch
Published: Wednesday, Sep 26, 2018

Joshua J. Meeks, MD, PhD

Joshua J. Meeks, MD, PhD

Bladder cancer researchers are still far away from fully understanding the genomics of the disease, according to Joshua J. Meeks, MD, PhD. While there is effort being put into understanding muscle-invasive bladder cancer (MIBC), the genomics of nonmuscle-invasive disease (NMIBC) are still obscure.

State of the Science Summit™ on Renal Cell Carcinoma and Bladder Cancer, Meeks, an assistant professor of urology, Northwestern University Feinberg School of Medicine, discussed the current understanding of genomics in bladder cancer.

OncLive: Could you discuss the genomic landscape of bladder cancer?

Meeks: We try to think about the framework of bladder cancer by looking at MIBC and NMIBC. There has been a lot more effort put into the MIBC setting. Gene expression profiling, whole-exome sequencing, methylomics, and regulons of more than 400 patients have been nicely detailed by The Cancer Genome Atlas (TCGA). [This] really looks at what is involved in these tumors, and it gave us so much insight into these cancers.

What is on the forefront for NMIBC, and how is it different? Certainly, there are less mutations, but it looks like it is different. There are some different pathways that are activated in these tumors that are not present in MIBC. How many of these are targetable? We also have to deal with the heterogeneity. It is almost as if they are starting from different places and going in different directions. Dealing with that heterogeneity and how to approach these tumors will be the next iteration of how we take this descriptive work and put it into place.

How does smoking status play into this?

We think about bladder cancer as a smoking-related cancer. One of the things that I was shocked by, when I first read the TCGA when it came out in 2014, was that the mutations that were in the smokers were the same exact mutations that were in the nonsmokers. It didn't make any sense to me. Our group took the TCGA data, which is publicly available, and we broke everything down to smoking and nonsmoking to look at the differences. We thought that they would be different, but we were shocked to find that the overall number of mutations was not different. It is very different in lung cancer; there is a much higher rate of mutations in smokers than nonsmokers.
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