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Recent studies suggest that cancer can arise from a cancer stem cell (CSC), a tumor-initiating cell that has properties similar to those of stem cells. CSCs have been identified in several malignancies, including those of blood, brain, and breast. Here, we test whether stem cell-like populations exist in human melanomas. In approximately 20% of the(More)
Dysregulated activation of Ras or its downstream effectors such as mitogen-activated protein kinase kinase and ERK has been shown to play a critical role in tumorigenesis of many cancer types. However, in melanoma, activating mutations in Ras are rarely observed and are limited to N-Ras in UV-exposed cells. In this study, we identify constitutively(More)
GenoMEL, comprising major familial melanoma research groups from North America, Europe, Asia, and Australia has created the largest familial melanoma sample yet available to characterize mutations in the high-risk melanoma susceptibility genes CDKN2A/alternate reading frames (ARF), which encodes p16 and p14ARF, and CDK4 and to evaluate their relationship(More)
Model organisms like Drosophila melanogaster or Caenorhabditis elegans have revealed genes that influence senescence and the evolvability of senescence. We are interested instead in evaluating why and how senescence evolves in natural populations. To do so, we are taking the ecological geneticist's perspective of comparing natural populations that differ in(More)
OBJECTIVES To determine if pathology review, within the context of a multidisciplinary pigmented lesion clinic, results in changes in diagnosis of melanocytic lesions and to ascertain if the change in diagnosis altered clinical management and outcome. METHODS Retrospective review of pathology reports, progress notes, and diagnoses entered in the(More)
BACKGROUND Malignant melanoma has been one of the most rapidly increasing cancers within the United States with few modifiable risk factors. This study investigates risk related to dietary factors, which are potentially modifiable. METHODS Newly diagnosed patients with melanoma (n = 502) were recruited from pigment lesion clinics and controls (n = 565)(More)
We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The(More)
A high melanocytic nevi count is the strongest known risk factor for cutaneous melanoma. We conducted a genome-wide association study for nevus count using 297,108 SNPs in 1,524 twins, with validation in an independent cohort of 4,107 individuals. We identified strongly associated variants in MTAP, a gene adjacent to the familial melanoma susceptibility(More)
We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75(More)