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
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Journal ArticleDOI
The immune-related role of BRAF in melanoma
Sara Tomei,Sara Tomei,Sara Tomei,Davide Bedognetti,Davide Bedognetti,Valeria De Giorgi,Michele Sommariva,Michele Sommariva,Sara Civini,Jennifer Reinboth,Jennifer Reinboth,Jennifer Reinboth,Muna Al Hashmi,Maria Libera Ascierto,Maria Libera Ascierto,Qiuzhen Liu,Ben D. Ayotte,Andrea Worschech,Lorenzo Uccellini,Lorenzo Uccellini,Paolo A. Ascierto,David S. Stroncek,Giuseppe Palmieri,Lotfi Chouchane,Ena Wang,Ena Wang,Francesco M. Marincola,Francesco M. Marincola +27 more
TL;DR: The role of BRAF and NRAS mutations in influencing the immune phenotype based on a classification previously identified by this group is explored.
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A comprehensive evaluation of pathogenic mutations in primary cutaneous melanomas, including the identification of novel loss-of-function variants.
Ivana Tichá,Jan Hojny,Romana Michálková,Ondrej Kodet,Eva Krkavcová,Nikola Hájková,Kristyna Nemejcova,Michaela Bartu,Radek Jaksa,Miroslav Dura,Madiha Kanwal,Andra S. Martinikova,Libor Macurek,Petra Zemankova,Zdenek Kleibl,Pavel Dundr +15 more
TL;DR: The results suggest that with the development of new therapeutic possibilities, not only BRAF testing, but complex molecular testing of cutaneous melanoma may become an integral part of the decision process concerning the treatment of patients with melanoma.
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BRAF inhibitor rechallenge in patients with advanced BRAF V600-mutant melanoma.
J. Roux,Cécile Pagès,Diane Malouf,Nicole Basset Seguin,Nika Madjlessi,Michel Baccard,Christelle Comte,A. Archimbaud,Maxime Battistella,Manuelle Viguier,Samia Mourah,Martine Bagot,Céleste Lebbé +12 more
TL;DR: It is suggested that intermittent treatment with BRAF inhibitors could provide clinical benefit and that sequential therapies should be further evaluated in clinical trials.
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Targeted therapy for melanoma: a primer.
TL;DR: The known mutations, amplifications, and deletions in kinase signaling pathways that have been implicated in melanoma; the prevalence of these genetic events in clinicopathologically defined melanoma subtypes; and the results of clinical trials that use targeted therapy approaches to block aberrantly activated pathways resulting from these mutations are reviewed.
Journal ArticleDOI
An Overview of the Changing Landscape of Treatment for Advanced Melanoma.
TL;DR: There have been a variety of new pharmacologic treatments for advanced melanoma including immunotherapy, targeted agents (BRAF and MEK inhibitors), and oncolytic viral therapy, with a focus on emerging therapies.
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
TL;DR: The implementation of array CGH is demonstrated to be able to measure copy number with high precision in the human genome, and to analyse clinical specimens by obtaining new information on chromosome 20 aberrations in breast cancer.
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