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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Activity of dasatinib against L576P KIT mutant melanoma: Molecular, cellular, and clinical correlates
Scott E. Woodman,Jonathan C. Trent,Katherine Stemke-Hale,Alexander J. Lazar,Sabrina Pricl,Giovanni M. Pavan,Maurizio Fermeglia,Y.N. Vashisht Gopal,Dan Yang,Donald A. Podoloff,Doina Ivan,Kevin B. Kim,Nicholas E. Papadopoulos,P. Hwu,Gordon B. Mills,Michael A. Davies,Michael A. Davies +16 more
TL;DR: In vitro testing showed that the cell viability of the L576P mutant cell line was not reduced by imatinib, nilotinib, or sorafenib small molecule KIT inhibitors effective in nonmelanoma cells with other KIT mutations, and thus has therapeutic implications for acrallentiginous, chronic sun-damaged, and mucosal melanomas.
Journal ArticleDOI
Epigenetic silencing of novel tumor suppressors in malignant melanoma.
Viswanathan Muthusamy,Sekhar Duraisamy,C. Matthew Bradbury,Cara Hobbs,David P. Curley,Betsy Nelson,Marcus Bosenberg +6 more
TL;DR: Reexpression of either of two of the silenced genes, HOXB13 and SYK, resulted in reduced colony formation in vitro and diminished tumor formation in vivo, indicating that these genes function as tumor suppressors in melanoma.
Journal ArticleDOI
Spectrum and Risk of Neoplasia in Werner Syndrome: A Systematic Review
TL;DR: The spectrum of neoplasia in Werner syndrome (WS) was defined using all case reports, and neoplasm type-specific risk in Japan WS patients was determined by calculating standardized incidence and proportionate incidence ratios (SIR and SPIR) relative to Osaka Japan prefecture incidence rates.
Journal ArticleDOI
The effects on human health from stratospheric ozone depletion and its interactions with climate change
Mary Norval,Anthony P. Cullen,F.R. de Gruijl,Janice Longstreth,Y Takizawa,Robyn M. Lucas,Frances P. Noonan,J.C. van der Leun +7 more
TL;DR: There is accumulating evidence that UVR exposure, either directly or via stimulation of vitamin D production, has protective effects on the development of some autoimmune diseases, including multiple sclerosis and type 1 diabetes.
Journal ArticleDOI
EZH2-Dependent Suppression of a Cellular Senescence Phenotype in Melanoma Cells by Inhibition of p21/CDKN1A Expression
Tao Fan,Shunlin Jiang,Nancy Chung,Ali Alikhan,Christina Ni,Chyi-Chia Richard Lee,Thomas J. Hornyak +6 more
TL;DR: A novel mechanism whereby EZH2 activation during tumor progression represses p21, leading to suppression of cellular senescence and enhanced tumorigenicity is described.
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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