First full sequencing of melanoma genome reveals several major cancer-causing genes

The complete genome of melanoma was recently sequenced by a research team at the National Institutes of Health, resulting in new identifications of cancer-related mutations and serving as a huge step forward towards cancer detection and subsequent treatment.

Melanoma is the most fatal form of skin cancer, caused by mutations of melanocytes, the cells that produce melanin. Two main risk factors include family history and sun exposure. Numerous genes scattered across the genome have been identified that increase the risk for developping melanoma. Overexposure to UV light can also lead to DNA damage, resulting in cancer-causing mutations in skin cells.

This study took a systematic approach towards identifying potential melanoma-causing genes by mapping out the entire genome of metastatic melanoma tumor samples and subsequently eliminating unlikely suspects.

The research team sequenced a total of 14 tumor samples with matching blood samples, using a technique known as whole-exome sequencing. They compared mutations observed in blood samples with those that occurred in the tumor tissue of the same individual in order to distinguish between somatic and inherited mutations.

Somatic mutations occur sporadically in tumor tissues. Of the somatic mutations, passenger mutations, which are mutations unlinked to tumor development, were excluded.

Melanoma-causing mutations that had already been identified in previous studies were left out. Based on both mutation rate and frequency, the likely candidates were identified.

Ionotropic glutamate receptor gene, GRIN2A, was recognized as the most highly mutated gene. It is suspected to be a tumor-suppressor gene, which is normally responsible for the prevention of uncontrolled cell growth. Mutation of tumor suppressor genes can often lead to cancer due to a lost ability to stop cell division.

TRRAP was identified as another likely possibility, because mutation of this gene was found in an exact position in six people with melanoma. Evidence suggests that TRRAP may be an oncogene. Oncogenes normally prevent apoptosis, or programmed cell death, during adverse conditions. Mutations of oncogenes often lead to cancer by causing uncontrollable cell growth.

TRRAP is naturally present in many species, implying that it is vital in maintaining normal cell functions.

Future experimentation involves further analysis of the glutamate signaling pathway in relation to melanoma.