ORIGINAL ARTICLES: Basic researchMelanoma candidate genes CDKN2A/p16/INK4A, p14ARF, and CDK4 sequencing in patients with uveal melanoma with relative high-risk for hereditary cancer predispositionAbdel-Rahman, Mohamed H.a,b; Pilarski, Robertb; Massengill, James B.a; Christopher, Benjamin N.a; Noss, Ryanb; Davidorf, Frederick H.aAuthor Information aDepartment of Ophthalmology bInternal Medicine and Comprehensive Cancer Center, Clinical Cancer Genetics Program, The Ohio State University, Columbus, Ohio, USA Correspondence to Mohamed H. Abdel-Rahman, MD, PhD, Department of Ophthalmology, Internal Medicine and Comprehensive Cancer Center, Clinical Cancer Genetics Program, The Ohio State University, 400 W 12th Avenue, Room 252N, Wiseman Hall, Columbus, Ohio 43210, USA Tel: +1 614 292 1396; fax: +1 614 247 7153; e-mail: [email protected] Supplementary digital content is available from the author at Received August 19, 2010 Accepted December 20, 2010 Melanoma Research: June 2011 - Volume 21 - Issue 3 - p 175-179 doi: 10.1097/CMR.0b013e328343eca2 Buy SDC Metrics AbstractIn Brief The reported frequencies of germline mutations in the melanoma candidate genes are low in patients with uveal melanoma (UM). However, the number of families studied is limited and the majority of the published reports used low-sensitivity techniques for mutational screening. Identifying the frequency of alterations in any of the melanoma genes in patients with UM with increased hereditary cancer risk is important for proper counseling of these patients. We studied a total of 47 patients with UM including three with a family history of UM, 18 with a family and/or personal history of cutaneous melanoma (CM), three with early age at diagnosis (<30), 11 with increased risk for a known familial cancer syndrome, and 12 with a second primary tumor. Germline screening for mutations in CDKN2A, p14ARF, and exon 2 of CDK4 was carried out by direct sequencing. We identified a variant (IVS1-69 C>T) of uncertain significance in exon 1b of p14ARF in one of the patients with UM and his mother who also had UM. The variant was neither detected in any of the other patients with UM nor in 146 controls. We did not identify pathogenic mutations in CDKN2A nor exon 2 of CDK4 gene. Our study supports the low frequency of germline mutation of the CM candidate genes in patients with UM with family histories suggestive of a high risk for hereditary cancer. Germline testing for CDKN2A might be reserved for patients with UM with a family history of two or more CM. Supplemental Digital Content is available in the article. © 2011 Lippincott Williams & Wilkins, Inc.