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Consensus on genomic classification of bladder cancer makes progress

The genomic revolution that followed the unraveling of the human genome has led to a push to classify cancer according to genetic and molecular – rather than cell and tissue – features. While some areas like breast cancer have made huge progress in this movement, bladder cancer is a relative latecomer.

To make progress in this area, seven centers of excellence around the world met at the Spanish National Cancer Research Centre (CNIO) in Madrid in March 2015 to discuss their various systems of classification of bladder cancer.

The meeting’s aim was to: review the classification strategies from each center, discuss areas of overlap, develop a co-operative approach to make best use of the classifications, and to collaborate on studies to validate them.

The seven groups in attendance were: The Cancer Genome Atlas (TCGA); Lund University in Sweden; three centers from the US: University of North Carolina, Baylor College of Medicine and MD Anderson Cancer Center; the CIT Consortium in France; and Spain’s CNIO.

The meeting reached consensus on one subtype. While the agreement marks a significant step toward a genomic classification of bladder cancer, the researchers say there is still a way to go to reach agreement on other subtypes.

A paper recently published in the journal Bladder Cancer describes the process and results of the meeting.

Lead author Seth P. Lerner, editor-in-chief of the journal and professor of urology at Baylor College of Medicine, says it is important to reach consensus about bladder cancer subtypes because it improves our understanding of the underlying biology of the disease.

Another reason why such a classification is important is because it improves treatment and management of patients – based either on differences in outcome or response to therapy. This second reason, notes Prof. Lerner, “concerns both standard and novel, targeted therapies towards precision medicine.”


Basal-squamous-like tumors BASQ characterized by four genes

At the meeting, the researchers from the seven centers agreed there is a subgroup of bladder cancer called basal-squamous-like tumors (BASQ).

The authors note that BASQ is characterized by high expression of the genes KRT5/6 and KRT14, and by low or undetectable expression of FOXA1 and GATA3 – a cluster that appears to be consistently associated with a poor prognosis.

The meeting also agreed there is another tumor subgroup with “urothelial differentiation features,” but there is currently not enough data to reach an optimal molecular definition.

A major event in the start and development of bladder cancer is loss of urothelial differentiation – where cells in the lining of the urinary tract do not acquire full functional behavior.

The researchers say more work is needed on this and other subtypes in order to best define them at the molecular level.

They also agreed some naming conventions for some types of bladder cancer and changes to some existing designations of tumor types to make it easier for groups to present proposals and findings at future meetings.

Commenting on the BASQ classification, Dr. Francisco X. Real, of the CNIO, recommends that:

“Future studies should refine this molecular definition, determine the optimal techniques that can be applied for tumor classification, as well as clinical-pathological and etiological associations.”

Like many cancers, once bladder cancer reaches an advanced stage, it is very difficult to treat, and chemotherapy is currently the only option.

In November 2014, Medical News Today learned about the first major step forward in the treatment of advanced bladder cancer for 30 years. The immunotherapy breakthrough, reported in Nature, concerns an antibody drug that helps the immune system find and kill cancer cells.

Written by Catharine Paddock