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
Melanoma treatment in review.
TL;DR: This review aims to survey therapies approved and under evaluation for melanoma treatment and relevant research on the molecular mechanisms underlying melanomagenesis.
Journal ArticleDOI
Phase II Study of the MEK1/MEK2 Inhibitor Trametinib in Patients With Metastatic BRAF-Mutant Cutaneous Melanoma Previously Treated With or Without a BRAF Inhibitor
Kevin B. Kim,Richard F. Kefford,Anna C. Pavlick,Jeffrey R. Infante,Antoni Ribas,Jeffrey A. Sosman,Leslie A. Fecher,Michael Millward,Grant A. McArthur,Patrick Hwu,Rene Gonzalez,Patrick A. Ott,Georgina V. Long,Olivia Gardner,Daniele Ouellet,Yanmei Xu,Douglas J. DeMarini,Ngocdiep T. Le,Kiran Patel,Karl D. Lewis +19 more
TL;DR: The response rate for the selective, allosteric MEK1/MEK2 inhibitor trametinib (GSK1120212), in patients with metastatic BRAF-mutant melanoma, and minimal clinical activity was observed as sequential therapy in patients previously treated with a BRAF inhibitor suggest that BRAf-inhibitor resistance mechanisms likely confer resistance to MEK- inhibitor monotherapy.
Journal ArticleDOI
Distinguishing Clinicopathologic Features of Patients with V600E and V600K BRAF-Mutant Metastatic Melanoma
Alexander M. Menzies,Lauren E. Haydu,Lydia Visintin,Lydia Visintin,Lydia Visintin,Matteo S. Carlino,Matteo S. Carlino,Julie Howle,Julie Howle,John F. Thompson,John F. Thompson,John F. Thompson,Richard F. Kefford,Richard F. Kefford,Richard A. Scolyer,Richard A. Scolyer,Georgina V. Long,Georgina V. Long +17 more
TL;DR: Different genotypes exist within BRAF-mutant metastatic melanoma, representing biologically and clinically discrete subtypes, suggesting distinct etiology and behavior.
Journal ArticleDOI
Fluorescence In Situ Hybridization (FISH) as an Ancillary Diagnostic Tool in the Diagnosis of Melanoma
Pedram Gerami,Susan Jewell,Larry E. Morrison,Beth Blondin,John Schulz,Teresa Ruffalo,Paul Matushek,Mona S. Legator,Kristine Jacobson,Scott R. Dalton,Susan Charzan,Nicholas A. Kolaitis,Joan Guitart,Terakeith Lertsbarapa,Susan L. Boone,Philip E. LeBoit,Boris C. Bastian +16 more
TL;DR: Sufficient chromosomal alterations are present in melanoma that a limited panel of FISH probes can distinguish most melanomas from most nevi, providing useful diagnostic information in cases that cannot be classified reliably by current methods.
Journal ArticleDOI
Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis
Sandra P. D'Angelo,James Larkin,Jeffrey A. Sosman,Céleste Lebbé,Benjamin Brady,Bart Neyns,Henrik Schmidt,Jessica C. Hassel,F. Stephen Hodi,Paul Lorigan,Kerry J. Savage,Wilson H. Miller,Peter Mohr,Ivan Marquez-Rodas,Julie Charles,Martin Kaatz,Mario Sznol,Jeffrey S. Weber,Alexander N. Shoushtari,Mary Ruisi,Joel Jiang,Jedd D. Wolchok +21 more
TL;DR: Nivolumab combined with ipilimumab seemed to have greater efficacy than either agent alone, and although the activity was lower in mucosal melanoma, the safety profile was similar between subtypes.
References
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Journal ArticleDOI
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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R: A Language for Data Analysis and Graphics
Ross Ihaka,Robert Gentleman +1 more
TL;DR: In this article, the authors discuss their experience designing and implementing a statistical computing language, which combines what they felt were useful features from two existing computer languages, and they feel that the new language provides advantages in the areas of portability, computational efficiency, memory management, and scope.
Journal ArticleDOI
A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4
TL;DR: P16 seems to act in a regulatory feedback circuit with CDK4, D-type cyclins and retinoblastoma protein, and inhibits the catalytic activity of theCDK4/cyclin D enzymes.
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Comparison of discrimination methods for the classification of tumors using gene expression data
TL;DR: Different discrimination methods for the classification of tumors based on gene expression data include nearest-neighbor classifiers, linear discriminant analysis, and classification trees, which are applied to datasets from three recently published cancer gene expression studies.
Journal ArticleDOI
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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