Previous investigation of Utah melanoma pedigrees resulted in the identification of the only major melanoma predisposition gene yet identified, cyclin-dependent kinase inhibitor 2A (CDKN2A or p16) (Cannon Albright et al., 1992; Cannon Albright et al., 1994; Kamb et al. 1994). However, only 20-40% of melanoma high-risk pedigrees have a p16 mutation, suggesting that additional melanoma predisposition genes exist. This is also supported by the existence of studied informative melanoma pedigrees that do not have mutations in the coding region of the p16 gene nor demonstrate linkage to the p16 locus on chromosome 9p21. The goal of this project is to identify additional melanoma predisposition genes through the genotypic characterization of Utah high-risk melanoma pedigrees which do not appear to be due to p16, ARF, or CDK4. This investigation will utilize resources that are unique to the University of Utah to identify non-p16 melanoma predisposition genes. These resources include 1) the Utah Population Database (UPDB), which permits identification and recruitment of numerous, extended high-risk melanoma pedigrees and facilitated investigation of the original Utah high-risk pedigree collection used to identify p16 and 2) a highly focused Familial Melanoma Research Clinic (FMRC) that is devoted to the clinical examination and molecular characterization of at-risk relatives in high-risk melanoma pedigrees. We will identify and sample high-risk melanoma pedigrees, perform a genomic search on the pedigrees with no indication of 9p involvement, and fine map any predisposition regions identified. Identification of melanoma predisposition genes will ultimately increase our ability to appropriately screen high-risk patients, and will suggest additional molecular pathways that may serve as targets for the diagnosis and treatment of melanoma.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA102422-05
Application #
7262570
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Seminara, Daniela
Project Start
2003-08-01
Project End
2010-05-31
Budget Start
2007-06-01
Budget End
2010-05-31
Support Year
5
Fiscal Year
2007
Total Cost
$490,073
Indirect Cost
Name
University of Utah
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Teerlink, Craig C; Huff, Chad; Stevens, Jeff et al. (2018) A Nonsynonymous Variant in the GOLM1 Gene in Cutaneous Malignant Melanoma. J Natl Cancer Inst :
Cannon-Albright, Lisa A; Teerlink, Craig C; Farnham, James M et al. (2013) Linkage analysis of extended high-risk pedigrees replicates a cutaneous malignant melanoma predisposition locus on chromosome 9q21. J Invest Dermatol 133:128-34
Teerlink, Craig; Farnham, James; Allen-Brady, Kristina et al. (2012) A unique genome-wide association analysis in extended Utah high-risk pedigrees identifies a novel melanoma risk variant on chromosome arm 10q. Hum Genet 131:77-85
Barrett, Jennifer H; Iles, Mark M; Harland, Mark et al. (2011) Genome-wide association study identifies three new melanoma susceptibility loci. Nat Genet 43:1108-13
Bishop, D Timothy; Demenais, Florence; Iles, Mark M et al. (2009) Genome-wide association study identifies three loci associated with melanoma risk. Nat Genet 41:920-5
Thomas, A; Camp, N J; Farnham, J M et al. (2008) Shared genomic segment analysis. Mapping disease predisposition genes in extended pedigrees using SNP genotype assays. Ann Hum Genet 72:279-87
Florell, Scott R; Meyer, Laurence J; Boucher, Kenneth M et al. (2008) Increased melanocytic nevi and nevus density in a G-34T CDKN2A/p16 melanoma-prone pedigree. J Invest Dermatol 128:2122-5
Goldstein, Alisa M; Chan, May; Harland, Mark et al. (2007) Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents. J Med Genet 44:99-106
Eliason, Mark J; Hansen, Chris B; Hart, Marybeth et al. (2007) Multiple primary melanomas in a CDKN2A mutation carrier exposed to ionizing radiation. Arch Dermatol 143:1409-12
Larson, April A; Leachman, Sancy A; Eliason, Mark J et al. (2007) Population-based assessment of non-melanoma cancer risk in relatives of cutaneous melanoma probands. J Invest Dermatol 127:183-8

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