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
Frequencies of BRAF and NRAS mutations are different in histological types and sites of origin of cutaneous melanoma: a meta-analysis.
TL;DR: This data indicates that the presence of BRAF and NRAS mutations in primary cutaneous melanoma is associated with atypical prognosis and the need to select patients for treatment with or without a prior BRAF or NRAS mutation.
Journal ArticleDOI
Cutaneous melanoma: From pathogenesis to therapy (Review)
Giulia Costanza Leonardi,Luca Falzone,Rossella Salemi,Antonino Zanghì,Demetrios A. Spandidos,James A. McCubrey,Saverio Candido,Massimo Libra +7 more
TL;DR: The epidemiological features of cutaneous melanoma along with the biological mechanisms involved in its development and progression are summarized and the current state-of-the-art of advanced stage melanoma treatment strategies and the currently available evidence of the use of predictive and prognostic biomarkers are discussed.
Journal ArticleDOI
Diagnosis and treatment of melanoma: European consensus-based interdisciplinary guideline
Claus Garbe,Ketty Peris,Axel Hauschild,Philippe Saiag,Mark R. Middleton,Alain Spatz,Jean-Jacques Grob,Josep Malvehy,Julia Newton-Bishop,Alexander J. Stratigos,Hubert Pehamberger,Alexander M.M. Eggermont +11 more
TL;DR: Recommendations on CM diagnosis and treatment are made based on systematic literature reviews and the experts' experience, with a clear survival benefit and the presence of toxicity limit its use in practice.
Journal ArticleDOI
Improving melanoma classification by integrating genetic and morphologic features.
Amaya Viros,Jane Fridlyand,Juergen Bauer,Konstantin Lasithiotakis,Claus Garbe,Daniel Pinkel,Boris C. Bastian +6 more
TL;DR: Refined morphological classification of primary melanomas can be used to improve existing melanoma classifications by forming subgroups that are genetically more homogeneous and likely to differ in important clinical variables such as outcome and pattern of metastasis.
Journal ArticleDOI
Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors
Narasimhan P. Agaram,Grace C. Wong,Tianhua Guo,Robert G. Maki,Samuel Singer,Ronald P. DeMatteo,Peter Besmer,Cristina R. Antonescu,Cristina R. Antonescu +8 more
TL;DR: It is hypothesis following the melanoma model that mutations in BRAF or NRAS may play a role in wild‐type GIST pathogenesis, and a primary BRAF V600E mutations in 7% of adult GIST patients, lacking KIT/PDGFRA mutations are identified.
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.
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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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