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
Ambiguous melanocytic tumors with loss of 3p21.
Iwei Yeh,Thaddeus W. Mully,Thomas Wiesner,Swapna S. Vemula,Sonia A. Mirza,Alyssa J. Sparatta,Timothy H. McCalmont,Boris C. Bastian,Philip E. LeBoit +8 more
TL;DR: B AP1 loss in a blue nevus–like melanoma is described and the histopathologic spectrum of spitzoid melanocytic neoplasms with BAP1 loss is expanded to include all cases with a single genomic event involving loss of the B AP1 locus.
Book ChapterDOI
MicroRNAs in Melanoma Biology
TL;DR: Findings further underscore the notion of a direct involvement of miRNAs in melanoma biology and the role of miRNA-target gene interactions in malignant melanoma.
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Genetics of melanoma progression: the rise and fall of cell senescence.
TL;DR: Current knowledge of the genetic or epigenetic driver changes necessary to generate a cutaneous metastatic melanoma, the commonest order in which these occur, and the relation of these changes to the biology and pathology of melanoma progression are analyzed are analyzed.
Journal ArticleDOI
Molecular cytogenetics of cutaneous melanocytic lesions - diagnostic, prognostic and therapeutic aspects.
TL;DR: Molecular cytogenetics of cutaneous melanocytic lesions – diagnostic, prognostic and therapeutic aspects and related aspects are studied.
Journal ArticleDOI
BRAF mutation analysis in circulating free tumor DNA of melanoma patients treated with BRAF inhibitors.
Maria Gonzalez-Cao,Clara Mayo-de-las-Casas,Miguel Angel Molina-Vila,Leticia De Mattos-Arruda,Eva Muñoz-Couselo,Jose Luis Manzano,Javier Cortes,J.P. Berros,Ana Drozdowskyj,Miguel F. Sanmamed,Alvaro Gonzalez,Carlos Alvarez,Santiago Viteri,Niki Karachaliou,Salvador Martin Algarra,Jordi Bertran-Alamillo,Núria Jordana-Ariza,Rafael Rosell +17 more
TL;DR: In 22 melanoma patients treated with BRAF inhibitors, the median progression-free survival was 3.6 years for those showing BRAFV600E in pretreatment cfDNA compared with 13.4 months for those in whom the mutation was not detected, indicating that the sensitive detection and accurate quantification of low-abundance BRAFv600E alleles in cfDNA using the assay can be useful for predicting treatment outcome.
References
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Mutations of the BRAF gene in human cancer
Helen Davies,Graham R. Bignell,Charles Cox,Philip J. Stephens,Sarah Edkins,S. M. Clegg,Jon W. Teague,Hayley Woffendin,Mathew J. Garnett,William Bottomley,Neil Davis,Ed Dicks,Rebecca Ewing,Yvonne Floyd,Kristian Gray,S. Hall,Rachel Hawes,Jaime Hughes,Vivian Kosmidou,Andrew Menzies,Catherine Mould,Adrian Parker,Claire Stevens,Stephen Watt,Steven Hooper,Rebecca Wilson,Hiran Jayatilake,Barry A. Gusterson,Colin Cooper,Janet Shipley,Darren Hargrave,Kathy Pritchard-Jones,Norman J. Maitland,Georgia Chenevix-Trench,Gregory J. Riggins,Darell D. Bigner,Giuseppe Palmieri,Antonio Cossu,Adrienne M. Flanagan,Andrew G. Nicholson,Judy W. C. Ho,Suet Yi Leung,Siu Tsan Yuen,Barbara L. Weber,Hilliard F. Seigler,Timothy L. Darrow,Hugh Paterson,Richard Marais,Christopher J. Marshall,Richard Wooster,Michael R. Stratton,P. Andrew Futreal +51 more
TL;DR: BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers, with a single substitution (V599E) accounting for 80%.
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Ross Ihaka,Robert Gentleman +1 more
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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
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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