Constitutional variants in POT1, TERF2IP, and ACD genes in patients with melanoma in the Polish population

Abstract

Evaluation of the prevalence of POT1, ACD, and TERF2IP mutations among Polish melanoma patients. A cohort of 60 patients from melanoma-prone families, 1500 unselected cases and 1500 controls were genotyped. Methodology included Sanger sequencing, in-silico software predilection, and TaqMan assays. We identified three nonsynonymous variants: POT1 c.903 G>T; TERF2IP c.970 A>G; and ACD c.1544 T>C and a splice site variant ACD c.645 G>A. The c.903 G>T was predicted to be pathogenic according to PolyPhen-2, benign according to Mutation Taster, PROVEAN, AGVGD, and SIFT. The c.645 G>A was defined as disease caused by Mutation Taster and Human Splicing Finder and as variant of unknown significance by ClinVar. The other detected variants were described as benign. The c.903 G>T variant was present in two unselected cases and one control [P = 0.57, odds ratio (OR) = 2.00]; the c.645 G>A variant was not detected among the unselected cases and the controls; the c.970 A>G variant was present in 110 cases and 133 controls (P = 0.14, OR = 0.81); the c.1544 T>C variant was present in 687 cases and 642 controls (P = 0.11, OR = 1.07). We found no loss of heterozygosity of the c.903 G>T, c.970 A>G, and c.645 G>A variants. C.645 G>A variant had no effect on splicing or expression. The changes in POT1 c.903 G>T and ACD c.645 G>A can be classified as rare variants of unknown significance, the other variants appear to be polymorphisms. Germline mutations in POT1, ACD, and TERF2IP are infrequent among Polish melanoma patients.