One step closer: Researchers identify gene that may increase susceptibility to malignant melanoma

December 1, 2008

Knowledge of the mechanisms involved in melanoma development may help to identify targets for chemoprevention or treatment. A variant in the cyclin D1 gene appears to increase susceptibility to malignant melanoma, an expert says.

Key Points

Cyclin D1 is a key regulator of the G1/S phase of the cell cycle, and its altered activity is associated with the development of several cancers, including melanoma.

Elevation of cyclin D1 protein levels as a result of either mutations in upstream genes or increases in the gene dosage represents a crucial event that drives progression in melanoma, says principal investigator Rachel J. Catarino, a Ph.D. candidate from the Portuguese Institute of Oncology, Porto, Portugal.

The investigators studied a variant of cyclin D1, A870G, by Polymerase Chain Reaction (PCR) technology in genomic DNA isolated from 161 individuals with melanoma and 892 healthy controls.

Persons carrying two G alleles, or two copies of the variant, were found to be 78 percent more likely to develop melanoma (P = .003).

Multivariate logistic regression analysis (adjusting for age and gender) confirmed the association between the presence of the GG cyclin D1 genotype and increased genetic susceptibility, Ms. Catarino tells Dermatology Times.

Function of G alleles

The two G alleles apparently have different functions. Isoform b is more efficient in terms of cellular transformation, i.e., it is a better oncogene. Isoform a is a better catalyst of phosphorylation and inactivation.

"The cyclin D1 polymorphism appears to be associated with a higher risk of melanoma, possibly by conferring growth advantages to cancer cells.

"We estimate the proportion of melanoma cases attributable to this genetic alteration to be 14 percent," Ms. Catarino says.

Knowledge of the mechanisms involved in melanoma development may help to identify targets for chemoprevention or treatment.

Commentary

Ulrich Keilholz, M.D., of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group and Charité Hospital, Berlin, says, "The results appear to be robust, though we don't see a gene dose effect. This study gives us another important piece to the puzzle of melanoma biology."

Disclosure: Ms. Catarino reports no relevant financial disclosures.