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
The molecular basis of melanomagenesis and the metastatic phenotype.
TL;DR: The genetics of melanoma and in particular the impact of genetic defects on dysregulation of the cell cycle are key issues in malignant transformation and are a major focus of this review.
Journal ArticleDOI
Melanoma biomarkers: current status and utility in diagnosis, prognosis, and response to therapy.
TL;DR: The utility of melanoma biomarkers for diagnosis and prognosis are discussed and how novel molecular signatures can help guide both melanoma diagnosis and therapy selection are suggested.
Journal ArticleDOI
Esophageal melanomas harbor frequent NRAS mutations unlike melanomas of other mucosal sites.
TL;DR: It is implied that esophageal melanomas have genetic alterations unique from those observed in other mucosal melanomas, but the prevalence of NRAS mutations was even higher than that of cutaneous melanomas.
Journal ArticleDOI
Clinical features and response to systemic therapy in a historical cohort of advanced or unresectable mucosal melanoma
Alexander N. Shoushtari,Mark J. Bluth,Debra A. Goldman,Christiana Bitas,Robert A. Lefkowitz,Michael A. Postow,Rodrigo Ramella Munhoz,Gauri Buchar,Robert Harrison Hester,Jacqueline A. Romero,Laura Fitzpatrick,Martin R. Weiser,Katherine S. Panageas,Jedd D. Wolchok,Paul B. Chapman,Richard D. Carvajal +15 more
TL;DR: Cytotoxic systemic therapy has modest activity in advanced/unresectable MM, belying its adjuvant benefit and brain imaging should be considered in routine surveillance.
Journal ArticleDOI
GLI2 cooperates with ZEB1 for transcriptional repression of CDH1 expression in human melanoma cells.
Carole Y. Perrot,Carole Y. Perrot,Carole Y. Perrot,Cristèle Gilbert,Cristèle Gilbert,Cristèle Gilbert,Véronique Marsaud,Véronique Marsaud,Véronique Marsaud,Antonio Postigo,Delphine Javelaud,Delphine Javelaud,Delphine Javelaud,Alain Mauviel,Alain Mauviel,Alain Mauviel +15 more
TL;DR: Evidence is provided thatGLI2 represses E‐cadherin gene (CDH1) expression in melanoma cells via distinct mechanisms, enhancing transcription of the EMT‐activator ZEB1 and cooperative repression of CDH1 gene transcription via direct binding of both GLI2 and Z EB1 to two closely positioned Kruppel‐like factor‐binding sites within the CDH 1 promoter.
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
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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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