Melanoma can metastasize at an early stage, and these metastases are typically resistant to medical treatment. In addition, melanoma is rising in incidence and mortality, greatly increasing the need for methods of prevention, early diagnosis, and treatment. Primary human cutaneous melanoma often has activating mutations in either NRAS or BRAF early in its progression; these activating mutations likely have a causal rather than simply correlative role in melanoma development; and evidence exists to support ultraviolet, in combination with genotypic and associated phenotypic susceptibilities, in the pathogenesis of somatic mutations in melanoma. We propose to determine the population-based frequencies of NRAS and BRAF somatic mutations in melanomas in a large international cohort and their associations with histologic subtypes, known risk factors, and prognostic indicators in melanoma. In addition, we will determine whether tumors from patients with second primary melanoma exhibit similar molecular classifications to the first primary. NRAS and BRAF mutational status will be characterized using a highly sensitive combination of laser capture microscopy and single strand conformational polymorphism analysis with direct manual sequencing of PCR products. Understanding of the role of these somatic mutations in the etiology and progression of melanoma likely will be crucial for its prevention, improved diagnosis, and effective application of new clinical treatments.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA112243-01
Application #
6859326
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Seminara, Daniela
Project Start
2005-05-13
Project End
2010-04-30
Budget Start
2005-05-13
Budget End
2006-04-30
Support Year
1
Fiscal Year
2005
Total Cost
$559,031
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Dermatology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Thomas, Nancy E; Edmiston, Sharon N; Orlow, Irene et al. (2018) Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes. J Invest Dermatol 138:2398-2404
Orlow, Irene; Shi, Yang; Kanetsky, Peter A et al. (2018) The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival. Pigment Cell Melanoma Res 31:287-296
Miles, Jonathan A; Orlow, Irene; Kanetsky, Peter A et al. (2018) Relationship of Chromosome Arm 10q Variants to Occurrence of Multiple Primary Melanoma in the Population-Based GEM Study. J Invest Dermatol :
Gibbs, D C; Ward, S V; Orlow, I et al. (2017) Functional melanoma-risk variant IRF4 rs12203592 associated with Breslow thickness: a pooled international study of primary melanomas. Br J Dermatol 177:e180-e182
Vernali, Steven; Waxweiler, Weston T; Dillon, Patrick M et al. (2017) Association of Incident Amelanotic Melanoma With Phenotypic Characteristics, MC1R Status, and Prior Amelanotic Melanoma. JAMA Dermatol 153:1026-1031
Schwitzer, Emily; Orlow, Irene; Zabor, Emily C et al. (2017) No association between prediagnosis exercise and survival in patients with high-risk primary melanoma: A population-based study. Pigment Cell Melanoma Res 30:424-427
Mauguen, Audrey; Zabor, Emily C; Thomas, Nancy E et al. (2017) Defining Cancer Subtypes With Distinctive Etiologic Profiles: An Application to the Epidemiology of Melanoma. J Am Stat Assoc 112:54-63
Luo, Li; Orlow, Irene; Kanetsky, Peter A et al. (2017) No prognostic value added by vitamin D pathway SNPs to current prognostic system for melanoma survival. PLoS One 12:e0174234
Thomas, Nancy E; Edmiston, Sharon N; Kanetsky, Peter A et al. (2017) Associations of MC1R Genotype and Patient Phenotypes with BRAF and NRAS Mutations in Melanoma. J Invest Dermatol 137:2588-2598
White, Kirsten A M; Luo, Li; Thompson, Todd A et al. (2016) Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study. Cancer Med 5:3336-3345

Showing the most recent 10 out of 61 publications