MITF gene variant associated with increased melanoma risk, high nevi count

Source: healio.com/dermatology, December 2105

A rare functional variant in the MITF gene was associated with increased melanoma risk, especially in patients with multiple primary melanoma, and high nevi count, according to study results recently published in JAMA Dermatology.

The gene MTIF variant p.E318K predisposes patients to melanoma and renal cell carcinoma, the researchers wrote. They studied the prevalence of MITF p.E318K in Spanish patents with melanoma, and its association with clinical and phenotypic features.

The researchers conducted a case-control study of 531 patients at the Melanoma Unit of Hospital Clinic of Barcelona, using TaqMan probes to genotype MITF p.E318K in all patients. There were 271 patients with multiple primary melanoma (MPM) affecting p16INK41 (wild-type p16INK4A), 191 probands from melanoma-prone families without mutations affecting p16INK4A and 69 patients with mutated p16INK4A.

A control group included 499 age-and sex-matched cancer-free people from the Spanish National Bank of DNA. Patient recruitment took place between Jan. 1, 1992, and June 30, 2014; with data analyzed between Sept. 1 and Nov. 30, 2014.

The prevalence of the MITF p.E318K variant was 1.9% in patients with melanoma and wild-type p16INK4A, 2.6% in patients with MPM, and 2.9% in patients with p16INK4A mutations, according to calculations of the MITF p.E318K variant among the subsets of patients.

Increased melanoma risk (odds ratio = 3.3; 95% CI, 1.43-7.43), especially in MPM (OR = 4.5; 95% CI, 1.83-11.01) and high nevi count, considered greater than 200 nevi (OR = 8.4; 95% CI, 2.14-33.19) were associated with MITF p.E318K. A dermatologic digital follow-up detected two fast-growing melanomas among two MITF p.E318K carriers.

“MITF (and MCIR gene) should be added to CDKN2A/CDK4 genetic testing based on published international recommendations for countries with low and high sun exposure,” the researchers concluded. “Genotyping for MITF (and MCIR) could be added to predictive testing for all relatives in CDKN2A-positive families. Strict dermatologic surveillance, periodic self-examination and renal cell carcinoma surveillance should be encouraged in this context” – by Bruce Thiel