Bladder cancer is one of the main causes of mortality worldwide. It is the fourth most prevalent type of cancer in men and the eleventh most prevalent in women. It is closely linked to smoking, although exposure to certain industrial chemical products in the workplace can also increase the risk of developing this cancer. It is more common in elderly patients and the estimated 5-year survival rate is 77.5%, although this number falls drastically in cases of locally advanced disease or metastasis.

Researchers from more than 40 centers around the world, including, as a noted author, the director of IMIM and associate professor of Harvard University, Dr. Joaquim Bellmunt, have taken part in TCGA (The Cancer Genome Atlas), which has drawn the map of the bladder cancer genome. This study provides a broader vision of the different varieties and alterations of bladder cancer and will allow for better treatments in the future.

One of the most thorough studies

Researchers have presented a thorough analysis of 412 invasive muscular bladder cancers, which they have analysed over a period of three years with 6 molecular profile platforms. This has allowed them to obtain a complete map of the different mutations that characterize the different types of tumour. They have identified 58 significantly mutated genes that were unknown to date and another 158 silenced genes that may become potential therapeutic targets.

At the same time, it has been possible to divide the different tumours in 5 subtypes according to their RNA. One of them, neuroendocrine, has never been described before and has a worse survival prognosis and many tumours in this subtype do not have evident small cells or show neuroendocrine histology under the microscope, thereby making diagnosis more difficult. However, the study has also identified mutations that make it possible to predict a 75% survival rate at 5 years.

These findings may help to choose personalized treatments based on the response and show a clear correlation with patient prognosis.

Understanding the cancer genome

TCGA is a project that began in 2005 and is supervised by two US institutions, the National Cancer Institute and the National Human Genome Research Institute, the object of which is to catalogue the genetic mutations responsible for cancer and to achieve a better understanding of this disease. To achieve this, the project uses genome sequencing techniques and bioinformatics.

The initial projects focused on glioblastoma multiforme, lung cancer and ovarian cancer. The second phase of TCGA aimed to characterize the genome of some twenty different types of tumour, a goal that was surpassed when they characterized the genome of 33 types, 10 of them rare tumours.

Reference article

Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G, Cherniack AD, Hinoue T, Laird PW, Hoadley KA, Akbani R, Castro MAA, Gibb EA, Kanchi RS, Gordenin DA, Shukla SA, Sanchez-Vega F, Hansel DE, Czerniak BA, Reuter VE, Su X, de Sa Carvalho B, Chagas VS, Mungall KL, Sadeghi S, Pedamallu CS, Lu Y, Klimczak LJ, Zhang J, Choo C, Ojesina AI, Bullman S, Leraas KM, Lichtenberg TM, Wu CJ, Schultz N, Getz G, Meyerson M, Mills GB, McConkey DJ; TCGA Research Network, Weinstein JN, Kwiatkowski DJ, Lerner SP. Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. Cell 2017; 171(3): 540-556.