25 genomes from metastatic melanomas sequenced

Summer is approaching and also good weather, sun and tanning.  We all like to get a flattering skin color but we have to be careful: this week a paper is published in Nature broadening our genetic knowledge about melanoma and also confirming the clear association between excess exposition to sun and the development of this cancer.

Patricia Krentcil and her (biological) daughter

Being very tanned is not always a synonym of beauty (this is clear when looking at the pic of Patricia Krentcil, who became famous after taking her little 5-year-old daughter to the solarium), but besides, too much sun exposure is the perfect ingredient to promote melanoma. Melanoma is the second most common cancer in young adults and it is notable because of its capacity to spread to far tissues and originate new malignant tumors in them (metastasis). If you catch it in early stages it has a very good prognosis, but if you don’t you have less than a 10% chance of surviving more than five years. It is because of these reasons that we need to deepen our knowledge about the molecular mechanisms that transform a melanocyte in a cancerous cell and what mutations are responsible for the aggressiveness of the tumor. All mutations get registered in the DNA sequence of cancer cells: the most important ones that cause and drive the development of the tumor and also those that do not contribute to the development of cancer but bear the imprints of the molecular processes that have generated them and as a consequence inform us about the origin and pathogenesis of cancer.

For the first time, 25 genomes from metastatic melanomas and the corresponding genomes of blood cells from the same patients have been sequenced.  Comparing them, researchers have obtained a genome-wide view of the changes suffered by the cell during cancer process in the different individuals. Melanomas coming from patients with chronic sun exposure contained up to 37 times more mutations than others coming from tissues with low solar exposure.

Besides, the researchers found out that PREX2 gene, that regulates the activity of a tumor suppressor gene, was mutated in a high percentage of the genomes analyzed and that surrounding the place of this gene in the chromosome (locus), there had been observed a considerable number of chromosomal rearrangements, that is, the chromosome was in this point highly disorganized and in many cases it was disordered because of a combination with other chromosomes.

To check if PREX2 is really important in the genesis of melanoma, scientists from MIT introduced human melanocytes containing 6 representative mutations of this gene into immune-deficient mice prone to develop tumors. In 4 out of 6 cases, these mice developed cancer faster than control ones (control mice had been transplanted melanocytes expressing the wild type version of PREX2). This way PREX2 is confirmed as a gene that facilitates the development of tumors in vivo.

Until now, two gene categories were important in cancer: oncogenes (when mutated they gain activity) or tumor suppressor genes (when mutated they lose their function and stop protecting the cell). PREX2 may represent a new gene category, as the mutations affecting PREX2 do not cause loss of function or gain of activity, rather mutations affecting PREX2 produce truncated proteins or protein variants that modify the original function of PREX2 and alter the cellular processes where this gene is involved.

Thanks to this paper, a genomic picture of the alterations suffered by the cell during processes of metastatic melanoma has been obtained. Understanding how these genomic aberrations contribute to the origin and progression of melanoma will help us to design more personalized treatments.  Meanwhile the best option is protecting yourself from the sun and check your skin periodically. Here there is a video that was released by David Cornfield Melanoma Fundation to make young people aware of the problem. The video is very emotional but it gives very good tips.  To those of you who do not want to see the video you can have a look at the abcd of melanoma.