Skin cancerConstitutional variants in POT1, TERF2IP, and ACD genes in patients with melanoma in the Polish populationMalińska, Karolinaa; Deptuła, Jakuba; Rogoża-Janiszewska, Emiliaa; Górski, Bohdana; Scott, Rodneyb; Rudnicka, Helenaa; Kashyap, Aniruddha; Domagała, Pawełc; Hybiak, Jolantac; Masojć, Bartłomiejd; Cybulski, Cezarya; Kram, Andrzejd; Boer, Magdalenae; Kiedrowicz, Magdalenae; Lubiński, Jana; Dębniak, Tadeusza Author Information aDepartment of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Szczecin, Poland bMedical Genetics, Faculty of Health, School of Biomedical Sciences and Pharmacy, University of Newcastle and the Hunter Medical Research Institute, Newcastle, Australia cDepartment of Pathology, Pomeranian Medical University in Szczecin dDepartment of Radiation Oncology, West Pomeranian Oncology Center in Szczecin, Szczecin eDepartment of Skin Diseases and Venerology PUM, Siedlecka, Poland Received 2 June 2020 Accepted 12 August 2020 Correspondence to Karolina Malińska, MSc, Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Unii Lubelskiej 1, 71-252 Szczecin, Poland, Tel: +48 91 441 72 05; e-mail: [email protected] European Journal of Cancer Prevention 29(6):p 511-519, November 2020. | DOI: 10.1097/CEJ.0000000000000633 Buy Metrics 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. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.