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
Mutational and functional analysis reveals ADAMTS18 metalloproteinase as a novel driver in melanoma.
Xiaomu Wei,Todd D. Prickett,Cristina G. Viloria,Alfredo A. Molinolo,Jimmy Lin,Isabel Cardenas-Navia,Pedro Cruz,Steven A. Rosenberg,Michael A. Davies,Jeffrey E. Gershenwald,Carlos López-Otín,Yardena Samuels +11 more
TL;DR: Melanoma cells expressing mutant ADAMTS18 had reduced cell migration after short hairpin RNA–mediated knockdown of ADAM TS18, suggesting that ADAMts18 mutations promote growth, migration, and metastasis in melanoma.
Journal ArticleDOI
Role of B-RafV600E in differentiated thyroid cancer and preclinical validation of compounds against B-RafV600E
TL;DR: B-Raf(V600E) is considered a marker of aggressive disease in both PTC (>1 cm) and micro-PTC, and interestingly, is associated with both loss of I-131 avidity and PTC recurrence.
Journal ArticleDOI
Lentigo Maligna: Melanoma In Situ on Chronically Sun-Damaged Skin
Jon A. Reed,Christopher R. Shea +1 more
TL;DR: A better understanding of the earliest stage of melanoma progression, including the contribution of chronic exposure to ultraviolet radiation, may lead to improved classification schemes that direct more effective targeted or personalized therapies for patients.
Journal ArticleDOI
Cutaneous Melanoma in Childhood and Adolescence Shows Frequent Loss of INK4A and Gain of KIT
Maria Daniotti,Andrea Ferrari,Simona Frigerio,Paola Casieri,Francesca Miselli,Elisa Zucca,Paola Collini,Gabriella Della Torre,Siranoush Manoukian,Bernard Peissel,Aldo Bono,Mario Santinami,Giorgio Parmiani,Licia Rivoltini,Silvana Pilotti,Monica Rodolfo +15 more
TL;DR: A c-Kit low-polysomy profile seems to parallel CDKN2A homozygous deletions in pediatric melanoma whereas the single activating mutation observed segregates with familial patients.
Journal ArticleDOI
Molecular analysis of a case of nevus of ota showing progressive evolution to melanoma with intermediate stages resembling cellular blue nevus.
TL;DR: Copy number changes typical of melanoma were identified by both FISH and CGH in the morphologically malignant areas illustrating the relationship of tumor progression and the progressive acquisition of genetic aberrations.
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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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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