IMIM - Institut Hospital del Mar d'Investigacions Mèdiques

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03/11/2017 - Press release

Hospital del Mar of Medical Research Institute involved in the largest international analysis for mapping the bladder cancer genome

The researchers have described 5 new bladder cancer subtypes, leading the way to personalised treatment possibilities.

Dr. Joaquim Bellmunt, director of the Hospital del Mar Medical Research Institute (IMIM) and Associate Professor at the University of Harvard, at Dana Farber Cancer Institute in Boston, is one of the first authors of a new international study that has mapped genome of bladder cancer. As part of the TCGA project (The Cancer Genome Atlas), the researchers have reported their final analysis of 412 tumour samples, providing the most accurate genetic description to date of this type of cancer. This will enable the analysis of new personalised treatment hypotheses for this disease.

The study was published in the journal Cell. Dr. Bellmunt has stated that thanks to this work, we now "have a much broader perspective on the different varieties of urinary bladder cancer and its genetic alterations". Even so, the head of the IMIM stresses that "it is necessary to continue researching the best treatments and confirm hypothesised new treatment methods." 

One of the most exhaustive studies

The researchers, numbering more than 40 and from different centres around the world, have presented an exhaustive analysis of 412 muscle-invasive bladder cancers, one of the highest numbers within the TCGA project (the previous study had only had 131 samples). The three-year-long analysis employed 6 molecular profiling platforms that enabled the scientists to obtain a complete map of the distinct mutations characterising the different types of tumours. In this way they identified 58 significantly mutated genes that were unknown up to now, and a further 158 silenced genes that could become potential therapeutic targets. This mutational load is associated with the APOBEC mutation signature (related to an enzyme that helps the body protect itself against viral infection).

In addition, RNA has been used to divide the various tumours into 5, one of which is described for the first time, denominated neuroendocrine, that has a poor survival prognosis and in which many of the tumours did not show clear small cells or neuroendocrine histology under the microscope, making the diagnosis difficult. On the other hand, the study has also identified mutations that predict 75% survival at 5 years.

These findings can be used to select response-based personalised treatments and they demonstrate a clear correlation with the prognostic evolution of the patients. As Dr. Bellmunt explains, this correlation "enables prognostic variables to be identified from a genomic perspective.” This can allow doctors to choose whether chemotherapy or immunotherapy is the best type of treatment for the different tumour subtypes.

Understanding the cancer genome

The TCGA project was initiated in 2005 and is supervised by two US institutes, the National Cancer Institute and the National Human Genome Research Institute. It is purpose is to catalogue the genetic mutations responsible for this disease and achieve a better understanding of cancer. To do this, the researchers use genome sequencing and bioinformatics techniques.

The first projects focused on glioblastoma multiforme, lung cancer, and ovarian cancer. The second phase of the TCGA was proposed to genomically characterise about twenty different types of tumours, a figure that was exceeded, the final number being 33, 10 of which are rare. The techniques used include gene expression profiling, copy number variation profiling, SNP genotyping, DNA methylation profiling throughout the genome, microRNA profiling, and exome sequencing of at least 1,200 genes.

Bladder cancer

Bladder cancer is the fourth most common cancer in men and the eleventh in women. The incidence and mortality rate is approximately 4 times higher among men. It is estimated that in 2015 more than 20,000 cases were diagnosed in Spain (data from the Spanish Society of Medical Oncology) and around 400,000 globally. Bladder cancer is strongly linked to smoking, although exposure to certain industrial chemicals in the workplace may also increase the risk of developing it.

Tumours of this kind are most commonly found in elderly patients. The mean diagnosis age is 73, and approximately 90% of patients are aged over 55. Survival at five years is estimated to be 77.5%, although this drops drastically in cases of locally advanced disease or metastasis.

Reference: Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, et al. Cell. 2017 Oct 4. pii: S0092-8674(17)31056-5. doi: 10.1016/j.Cell.2017.09.007. PMID: 28988769

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