Cutaneous melanoma susceptibility and progression genes

Snoo, Femke A. de; Hayward, Nicholas K.

doi:10.1016/j.canlet.2004.12.033

Cited by 106 publications

(112 citation statements)

References 245 publications

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“…Mutations in CDK4 are rare. [6][7][8][9][10][11] The differences in the incidence of melanoma and penetrance of CDKN2A mutations among countries are such that there is no single guideline for genetic testing that could be applied worldwide. 12,13 Leachman et al 13 proposed that 2 cancer events, including pancreatic cancer, either in the patient or in a family member, are criteria enough to best identify which patients would benefit from genetic testing in low melanoma incidence areas.…”

Section: Discussionmentioning

confidence: 99%

Multiple primary melanomas (MPMs) and criteria for genetic assessment: MultiMEL, a multicenter study of the Italian Melanoma Intergroup

Bruno

Pastorino

Ghiorzo

et al. 2016

Journal of the American Academy of Dermatology

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Background: Multiple primary melanoma (MPM), in concert with a positive family history, is a predictor of cyclin-dependent kinase (CDK) inhibitor 2A (CDKN2A) germline mutations. A rule regarding the presence of either 2 or 3 or more cancer events (melanoma and pancreatic cancer) in low or high melanoma incidence populations, respectively, has been established to select patients for genetic referral.

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Section: Discussionmentioning

confidence: 99%

Multiple primary melanomas (MPMs) and criteria for genetic assessment: MultiMEL, a multicenter study of the Italian Melanoma Intergroup

Bruno

Pastorino

Ghiorzo

et al. 2016

Journal of the American Academy of Dermatology

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“…1). Elucidation of such genes has important implications for defining melanoma subtypes (2) and for tailoring treatment (e.g., MEK, KIT, or BRAF inhibitors).…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Loss of Heterozygosity and Copy Number Analysis in Melanoma Using High-Density Single-Nucleotide Polymorphism Arrays

2007

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Although a number of genes related to melanoma development have been identified through candidate gene screening approaches, few studies have attempted to conduct such analyses on a genome-wide scale. Here we use Illumina 317K whole-genome single-nucleotide polymorphism arrays to define a comprehensive allelotype of melanoma based on loss of heterozygosity (LOH) and copy number changes in a panel of 76 melanoma cell lines. In keeping with previous reports, we found frequent LOH on chromosome arms 9p (72%), 10p (55%), 10q (55%), 9q (49%), 6q (43%), 11q (43%), and 17p (41%). Tumor suppressor genes (TSGs) can be identified through homozygous deletion (HD). We detected 174 HDs, the most common of which targeted CDKN2A (n = 33). The second highest frequency of HD occurred in PTEN (n = 8), another well known melanoma TSG. HDs were also common for PTPRD (n = 7) and HDAC4 (n = 3), TSGs recently found to be mutated or deleted in other cancer types. Analysis of other HDs and regions of LOH that we have identified might lead to the characterization of further melanoma TSGs. We noted 197 regional amplifications, including some centered on the melanoma oncogenes MITF (n = 9), NRAS (n = 3), BRAF

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“…The MAPK pathway is activated through mutation of BRAF in 62% to 72% of sporadic melanomas and by RAS mutations in about 10% (7,8). The relationship between MAPK activation and UVR exposure is complex.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous and UV Radiation–Induced Multiple Metastatic Melanomas in Cdk4R24C/R24C/TPras Mice

et al. 2006

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Human melanoma susceptibility is often characterized by germ-line inactivating CDKN2A (INK4A/ARF) mutations, or mutations that activate CDK4 by preventing its binding to and inhibition by INK4A. We have previously shown that a single neonatal UV radiation (UVR) dose delivered to mice that carry melanocyte-specific activation of Hras (TPras) increases melanoma penetrance from 0% to 57%. Here, we report that activated Cdk4 cooperates with activated Hras to enhance susceptibility to melanoma in mice. Whereas UVR treatment failed to induce melanomas in Cdk4 R24C/R24C mice, it greatly increased the penetrance and decreased the age of onset of melanoma development in Cdk4 R24C/R24C /TPras animals compared with TPras alone. This increased penetrance was dependent on the threshold of Cdk4 activation as Cdk4 R24C/+ / TPras animals did not show an increase in UVR-induced melanoma penetrance compared with TPras alone. In addition, Cdk4 R24C/R24C /TPras mice invariably developed multiple lesions, which occurred rarely in TPras mice. These results indicate that germ-line defects abrogating the pRb pathway may enhance UVR-induced melanoma. TPras and Cdk4 R24C/R24C /TPras tumors were comparable histopathologically but the latter were larger and more aggressive and cultured cells derived from such melanomas were also larger and had higher levels of nuclear atypia. Moreover, the melanomas in Cdk4 R24C/R24C /TPras mice, but not in TPras mice, readily metastasized to regional lymph nodes. Thus, it seems that in the mouse, Hras activation initiates UVRinduced melanoma development whereas the cell cycle defect introduced by mutant Cdk4 contributes to tumor progression, producing more aggressive, metastatic tumors.

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Cutaneous melanoma susceptibility and progression genes

Cited by 106 publications

References 245 publications

Multiple primary melanomas (MPMs) and criteria for genetic assessment: MultiMEL, a multicenter study of the Italian Melanoma Intergroup

Multiple primary melanomas (MPMs) and criteria for genetic assessment: MultiMEL, a multicenter study of the Italian Melanoma Intergroup

Genome-Wide Loss of Heterozygosity and Copy Number Analysis in Melanoma Using High-Density Single-Nucleotide Polymorphism Arrays

Spontaneous and UV Radiation–Induced Multiple Metastatic Melanomas in Cdk4R24C/R24C/TPras Mice

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