10:15pm Tuesday 12 December 2017

A new genetic mechanism contributing to bladder cancer

It is generally considered that the alterations found in solid tumours of the adult arise during adulthood. A study directed by investigators of the Molecular Pathology Programme at the CNIO, in close collaboration with physicians from the Hospital del Mar‐IMIM (Barcelona) and the University of Regensburg (Germany), shows for the first time, that postzygotic activating mutations in the HRAS oncogene, occurring during embryonic development, can contribute to cancer of the adult, more specifically to bladder tumours.

The study was carried out in a patient who was found to be a “mosaic” of cells harbouring normal HRAS and mutant HRAS sequences; mosaicism affected all three germ layers. The patient was identified because he had an extensive congenital hyperkeratotic proliferative skin lesion, known as epidermal nevus, and presented with multiple urothelial tumours, the first of which was diagnosed at an unusual young age.

These findings have potential implications at both basic and clinical levels. At the basic level, they indicate that some mutations found in adult cancers may have occurred during embryonic life, highlighting the relevance of understanding their cause and nature and whether they can be prevented. Mosaicism of other genomic alterations was also recently identified by the CNIO group and collaborators in blood leukocytes of control individuals as well as in subjects with bladder cancer (Rodríguez‐Santiago et al., Am J Human Genet 2010; 87:129‐138).

At the clinical level, the findings raise the question of whether subjects with epidermal nevi (approximately 0.2% of the population) might benefit from closer clinical follow‐up to rule out cancer development.

Article Reference:

A Hratfinceler Cre, fTeorlel nAc, eR:e al FX. HRAS Mutation Mosaicism Causing Urothelial Cancer and
Epidermal Nevus. N Eng J Med 2011; (In press).


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