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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Phase II Trial of MEK Inhibitor Selumetinib (AZD6244, ARRY-142886) in Patients with BRAFV600E/K-Mutated Melanoma
Federica Catalanotti,David B. Solit,Melissa Pulitzer,Michael F. Berger,Sasinya N. Scott,Tunc Iyriboz,Mario E. Lacouture,Katherine S. Panageas,Jedd D. Wolchok,Richard D. Carvajal,Gary K. Schwartz,Neal Rosen,Paul B. Chapman +12 more
TL;DR: The results provide rationale for co-targeting MEK and PI3K/AKT in patients with BRAF mutant melanoma whose tumors express high pAKT, but the complexity of genetic changes in melanoma indicates that additional genetic information will be needed for optimal selection of patients likely to respond to MEK inhibitors.
Journal ArticleDOI
Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases.
Béatrice Vergier,Martina Prochazkova-Carlotti,Arnaud de la Fouchardière,Lorenzo Cerroni,Daniela Massi,Vincenzo De Giorgi,Christiane Bailly,Ulrich Wesselmann,Apollon Karlseladze,Marie-Françoise Avril,Thomas Jouary,Jean-Philippe Merlio +11 more
TL;DR: The value of this FISH test is to add a reproducible demonstration of malignancy to the histopathological diagnosis, especially in doubtful/ambiguous melanocytic tumors, allowing such tumors to be managed as melanomas.
Journal ArticleDOI
Dabrafenib and its potential for the treatment of metastatic melanoma
TL;DR: Dabrafenib appears similar to vemurafenib with regard to efficacy but it is associated with less toxicity, and it is expected that new combinations of targeted drugs, such as the combination of dabrafenIB and trametinib (GSK1120212, a MEK inhibitor), will provide higher response rates and more durable clinical benefit than dabrafENib monotherapy.
Journal ArticleDOI
Genomic profiling of malignant melanoma using tiling-resolution arrayCGH.
Göran Jönsson,Christina Dahl,Johan Staaf,T Sandberg,Pär-Ola Bendahl,Markus Ringnér,Per Guldberg,Åke Borg +7 more
TL;DR: For the first time, alterations of the various melanoma genes were associated with distinct chromosomal imbalances suggestive of specific genomic programs in melanoma development.
Journal ArticleDOI
Classifying ambiguous melanocytic lesions with FISH and correlation with clinical long-term follow up.
Timo Gaiser,Timo Gaiser,Heinz Kutzner,Gabriele Palmedo,Markus D. Siegelin,Markus D. Siegelin,Thomas Wiesner,Thomas Bruckner,Wolfgang Hartschuh,Alexander Enk,Maria Becker +10 more
TL;DR: The FISH technique with its present composition of locus-specific probes for RREB1/MYB and CCND1 did not achieve a clinically useful sensitivity and specificity, and a reassessment of the probes and better standardization of the method may lead to a valuable diagnostic tool.
References
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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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