Genetic Mutations Associated with Human Melanoma

As we have described in previous articles, there is a strong association between cancer and genetic mutations that disrupt the normal constraints placed upon cell growth and division.  In this article, evidence will be presented that links a particular set of unusual genetic mutations with human melanoma. 

Melanoma is a particularly deadly cancer of the skin.  The cells that become cancerous in melanoma are the so-called melanocytes that elaborate melanin – the pigment responsible for skin color.  The precise etiology of melanoma is not known; however, exposure to ultraviolet (UV) radiation either from natural sunlight or derived artificially from tanning beds increases the risk of developing this cancer.  The particular danger inherent in melanoma is the propensity of cancerous cells to travel from the initial site of development to other tissues of the body – a process referred to as metastasis.  It is therefore important to detect the presence of the cancerous mass before it has the opportunity to spread.

The research to date has revealed that most genetic mutations associated with various cancers seem to reside within the protein-coding regions of genes or at the splice junctions.  However Dr. Franklin W. Huang and his colleagues at the Broad Institute of Harvard and MIT, Cambridge MA were interested in determining whether any mutations consistent with tumor production appeared outside of the protein-coding regions.

To arrive at an answer to this question, the investigators performed an exhaustive analysis of whole-genome sequencing data from 70 individual cancerous melanomas.  From this analysis they discovered two independent mutations that reside within the promoter region – the promoter region of the genome lies outside of the protein coding region of the genes and is responsible for the initiation of gene transcription – for that region of the genome responsible for the production of the telemorase reverse transcriptase enzyme (TERT).  These mutations were found in 71% of the melanomas examined – this represents a remarkably high association.    In addition, they found an elevated frequency of these mutations in human bladder and liver cancer cells grown in culture.  TERT is of particular significance because this enzyme is responsible for lengthening telomeres in DNA strands and promoting cells to grow out of control.  It would, therefore, be a reasonable candidate for the mechanism of tumorigenesis.