Journal ArticleDOI
Distinct Sets of Genetic Alterations in Melanoma
John A. Curtin,Jane Fridlyand,Toshiro Kageshita,Hetal N. Patel,Klaus J. Busam,Heinz Kutzner,Kwang Hyun Cho,Setsuya Aiba,Eva B. Bröcker,Philip E. LeBoit,Daniel Pinkel,Boris C. Bastian +11 more
TLDR
The genetic alterations identified in melanoma at different sites and with different levels of sun exposure indicate that there are distinct genetic pathways in the development of melanoma and implicate CDK4 and CCND1 as independent oncogenes in melanomas without mutations in BRAF or N-RAS.Abstract:
Background Exposure to ultraviolet light is a major causative factor in melanoma, although the relationship between risk and exposure is complex. We hypothesized that the clinical heterogeneity is explained by genetically distinct types of melanoma with different susceptibility to ultraviolet light. Methods We compared genome-wide alterations in the number of copies of DNA and mutational status of BRAF and N-RAS in 126 melanomas from four groups in which the degree of exposure to ultraviolet light differs: 30 melanomas from skin with chronic sun-induced damage and 40 melanomas from skin without such damage; 36 melanomas from palms, soles, and subungual (acral) sites; and 20 mucosal melanomas. Results We found significant differences in the frequencies of regional changes in the number of copies of DNA and mutation frequencies in BRAF among the four groups of melanomas. Samples could be correctly classified into the four groups with 70 percent accuracy on the basis of the changes in the number of copies of...read more
Citations
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Journal ArticleDOI
High Frequency of p16INK4A Promoter Methylation in NRAS-Mutated Cutaneous Melanoma
TL;DR: Interestingly, p16(INK4A) promoter methylation was significantly overrepresented in NRAS-mutated samples compared to NRAS wild-type samples (P=0.0004), indicating an association between these two events.
Journal ArticleDOI
Spitz nevi, atypical spitzoid neoplasms, and spitzoid melanoma.
TL;DR: The clinical and histopathological attributes of Spitz nevi and spitzoid melanoma are reviewed and molecular assessment by way of comparative genomic hybridization or fluorescence in situ hybridization is increasingly used to facilitate assessment of this challenging differential and is especially germane to the evaluation of ambiguous lesions.
Journal ArticleDOI
Osteopontin is a downstream effector of the PI3-kinase pathway in melanomas that is inversely correlated with functional PTEN
Leisl M. Packer,Sandra Pavey,Andrew Parker,Mitchell S. Stark,Peter Johansson,B. E. Clarke,Pamela M. Pollock,Markus Ringnér,Nicholas K. Hayward +8 more
TL;DR: Osteopontin (OPN), a secreted glycophosphoprotein that contributes to tumor progression, was more abundant at both the mRNA and protein level in PTEN mutants, indicating that OPN acts downstream of PI3K in melanoma and provides insight into how PTEN loss contributes to melanoma development.
Journal ArticleDOI
Malignant melanoma of sun-protected sites: a review of clinical, histological, and molecular features.
Emily A. Merkel,Pedram Gerami +1 more
TL;DR: To better understand non-UV-mediated pathogenesis in melanoma, a joint literature review of clinical, histological, and molecular features in acral and mucosal melanoma was conducted and aberrations in KIT, PDGFRA, TERT, and other commonly involved genes were reviewed.
Journal ArticleDOI
New drug targets in metastatic melanoma
Blanca Homet,Antoni Ribas +1 more
TL;DR: Current molecular targeted treatment options, immunotherapy and promising ongoing research to develop new strategies to treat melanoma are discussed.
References
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Mutations of the BRAF gene in human cancer
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A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4
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Comparison of discrimination methods for the classification of tumors using gene expression data
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High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays
Daniel Pinkel,Daniel Pinkel,Richard Segraves,Damir Sudar,Steven M. Clark,Ian Poole,David Kowbel,Colin Collins,Wen Lin Kuo,Chira Chen,Ye Zhai,Shanaz H. Dairkee,Britt-Marie Ljung,Joe W. Gray,Joe W. Gray,Donna G. Albertson,Donna G. Albertson,Donna G. Albertson +17 more
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