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
In vivo microscopic features of nodular melanomas: Dermoscopy, confocal microscopy, and histopathologic correlates
Sonia Segura,Giovanni Pellacani,Susana Puig,Caterina Longo,Sara Bassoli,Pascale Guitera,Josep Palou,Scott W. Menzies,Stefania Seidenari,Josep Malvehy +9 more
TL;DR: Distinctive dermoscopic and confocal features seen in NMs compared with SSMs are helpful in making the diagnosis and suggest different biological behavior.
Journal ArticleDOI
Mutation landscape in melanoma patients clinical implications of heterogeneity of BRAF mutations
Lucie Heinzerling,M Baiter,S Kühnapfel,Gerhard Schuler,P Keikavoussi,Abbas Agaimy,Franklin Kiesewetter,A. Hartmann,Regine Schneider-Stock +8 more
TL;DR: As heterogeneity with respect to BRAF mutation status is detected in melanoma patients, subsequent testing of initially wild-type patients can yield different results and thus make BRAF inhibitor therapy accessible, and the role of heterogeneity in testing and for clinical response to therapy with a BRAF inhibitors needs to be further investigated.
Journal ArticleDOI
Cutaneous Toxic Effects Associated With Vemurafenib and Inhibition of the BRAF Pathway
TL;DR: 3 cases are presented that highlight the development of squamous cell carcinomas and other cutaneous sequelae that have not been previously reported and are reminiscent of those observed with administration of the multikinase inhibitor sorafenib tosylate.
Journal ArticleDOI
A Phase II Trial of Sorafenib in Metastatic Melanoma with Tissue Correlates
Patrick A. Ott,Anne Hamilton,Anne Hamilton,Christina Min,Sara Safarzadeh-Amiri,Lauren Goldberg,Joanne Yoon,Herman Yee,Michael T Buckley,Paul J. Christos,John Wright,David Polsky,Iman Osman,Leonard Liebes,Anna C. Pavlick +14 more
TL;DR: Sorafenib monotherapy has limited activity in advanced melanoma patients and BRAFV600E mutational status of the tumor was not associated with clinical activity and no significant effect of sorAFenib on cyclin D1 or Ki67 was seen, suggesting that sorafenIB is not an effective BRAF inhibitor or that additional signaling pathways are equally important in the patients who benefit from sorafinib.
Journal ArticleDOI
Role of UV in cutaneous melanoma.
TL;DR: The dual role of the melanin pigment as a photoprotector as well as a photosensitizer is evaluated and the evidence for association between melanin levels (constitutive and induced) and melanoma risk is examined.
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
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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
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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