A new gene discovery may represent a new diagnostic marker or even therapeutic target for rare, aggressive acral lentiginous melanoma (ALM), researchers report in Genome Research (Apr. 2017; 27:524–532).
The authors note that the understanding of non-ultraviolet (UV)-derived cutaneous melanomas (CM) remains limited. In the paper they suggest that a deeper analysis of ALM, a rare sun-shielded melanoma subtype associated with poorer survival than CM, is needed to better understand the non-UV mechanisms behind the development of some skin cancers.
Investigators conducted comprehensive genomic and transcriptomic analysis of samples from 34 patients with ALM, and found significant evidence that inhibiting a protein called TERT may be “an effective approach” to destroying ALM cells.
“These findings provide insight into the role TERT plays in the formation of ALM, and reveal preliminary evidence that inhibiting TERT has a deadly effect on ALM cancer cells,” Dr. Jeffrey Trent, President and Research Director at the Translational Genomics Research Institute in Phoenix, Arizona, one of three senior authors of the study, said in a press release.
Genetic changes in TERT were found among 41% of the patients in this study, which the authors say suggests that additional research should be undertaken to verify the impact of genetic aberrations on TERT activity.
In laboratory experiments, more than 75% of ALM cancer cells were affected, following 72 hours of exposure to a drug that inhibits TERT.
“These data establish a foundation for understanding ALM’s genetic triggers, with the ultimate goal to inform ALM clinical management for patients,” Dr. Jeffrey Sosman, one of the paper’s co-senior authors and co-leader of the Translational Research in Solid Tumors (TRIST) Program and Director of the Melanoma Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, and a professor at the Feinberg School of Medicine, said in the release.
The authors note that while much is known about the pathology of the more common cutaneous melanoma—including the impact of UV radiation and the BRAF gene—much less is known about ALM. ALM typically arises on sun-shielded areas of the skin, such as the palms of hands, the soles of feet, and fingernail and toenail beds, and is more prevalent than CM among people with darker skin pigmentations.