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
Characterization of candidate gene copy number alterations in the 11q13 region along with BRAF and NRAS mutations in human melanoma.
Viktória Lázár,Szilvia Ecsedi,Attila G Szöll odblac,si,Reka Toth,Laura Vízkeleti,Zsuzsa Rákosy,Zsuzsa Rákosy,Ágnes Bégány,Róza Ádány,Róza Ádány,Margit Balázs,Margit Balázs +12 more
TL;DR: It is assumed that coamplification of these candidate genes in the 11q13 region or CCND1 gene alterations along with either BRAF or NRAS mutations might be more important for prognosis than the presence of these alterations alone.
Journal ArticleDOI
Polymorphisms in nevus-associated genes MTAP, PLA2G6, and IRF4 and the risk of invasive cutaneous melanoma.
Marina Kvaskoff,David C. Whiteman,Zhen Zhen Zhao,Grant W. Montgomery,Nicholas G. Martin,Nicholas K. Hayward,David L. Duffy +6 more
TL;DR: The results suggest that the relationship between MTAP and melanoma is subtype-specific, and that the association between IRF4 and melanomas is more evident for cases with a younger age at onset, and lend some support to the ‘divergent pathways’ hypothesis.
Journal ArticleDOI
Distinct subclonal tumour responses to therapy revealed by circulating cell-free DNA.
Gabriela Gremel,Rebecca Lee,Maria Romina Girotti,A. Mandal,Sara Valpione,G Garner,Mahmood Ayub,S. Wood,Dominic G. Rothwell,Alberto Fusi,Andrew L. Wallace,Ged Brady,Caroline Dive,Nathalie Dhomen,Paul Lorigan,Richard Marais +15 more
TL;DR: Next-generation sequencing of cfDNA is used to monitor therapy responses of a metastatic vaginal mucosal melanoma and shows that cfDNA can be used tomonitor tumour evolution and subclonal responses to therapy even when biopsies are not available.
Journal ArticleDOI
Personalized Clinical Trials in Hepatocellular Carcinoma Based on Biomarker Selection.
Bingnan Zhang,Richard S. Finn +1 more
TL;DR: Clinical development of new agents in HCC will need to be targeted towards those patients who are most likely to benefit, and based on biomarkers for patient selection, this strategy is more likely to yield positive results and mitigate the risk of continued negative Phase III studies.
Journal ArticleDOI
Regulation of NR4A nuclear receptor expression by oncogenic BRAF in melanoma cells.
TL;DR: In this article, the BRAF-MEK-ERK cascade was used to detect mutations in the MAPK pathway effectors, NRAS or BRAF, which are detected in over 70% of melanoma cells.
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
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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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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