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
Ultraviolet exposure and risk of melanoma and basal cell carcinoma in Ulm and Dresden, Germany
Peter Kaskel,U. Lange,S. Sander,M. Huber,Jochen Utikal,Jochen Utikal,Jochen Utikal,Ulrike Leiter,Ulrike Leiter,Gertraud Krähn,Michael Meurer,Martina Kron +11 more
TL;DR: There is a perpetuating increase in melanoma and basal cell carcinoma incidence in Europe and few studies are evaluating various risk factors for both tumours.
Journal ArticleDOI
AMPK promotes survival of c‐Myc‐positive melanoma cells by suppressing oxidative stress
Alain Kfoury,Marzia Armaro,Caterina Collodet,Caterina Collodet,Jessica Sordet-Dessimoz,Maria Pilar Giner,Stefan Christen,Sofia Moco,Marion Leleu,Laurence de Leval,Ute Koch,Andreas Trumpp,Kei Sakamoto,Kei Sakamoto,Friedrich Beermann,Freddy Radtke +15 more
TL;DR: The NrasQ61KINK4a−/− mouse melanoma model is used to show that c‐Myc is essential for tumor initiation, maintenance, and metastasis, and TCGA database analysis of early‐stage human melanoma samples revealed an inverse correlation between C‐MyC and patient survival, suggesting that C‐MYC expression levels could serve as a prognostic marker for early-stage disease.
Journal ArticleDOI
In silico modeling predicts drug sensitivity of patient-derived cancer cells
Sandeep C. Pingle,Zeba Sultana,Sandra Pastorino,Pengfei Jiang,Rajesh Mukthavaram,Ying Chao,Ila Sri Bharati,Natsuko Nomura,Milan Makale,Taher Abbasi,Shweta Kapoor,Ansu Kumar,Shahabuddin Usmani,Ashish Kumar Agrawal,Shireen Vali,Santosh Kesari +15 more
TL;DR: By accurately predicting responses of cancer cells to targeted agents a priori, this in silico tumor model provides an innovative approach to personalizing therapy and promises to improve clinical management of cancer.
Journal ArticleDOI
Vemurafenib for the treatment of melanoma
Emmet Jordan,Catherine M. Kelly +1 more
TL;DR: Vemurafenib is an oral agent licensed for patients with BRAF V600E mutation-positive inoperable and metastatic melanoma and the most common adverse effects observed in Phase III clinical trials were dermatological events, arthralgia and fatigue.
Journal ArticleDOI
Use of integrative epigenetic and cytogenetic analyses to identify novel tumor-suppressor genes in malignant melanoma.
TL;DR: Twenty-seven genes were identified in areas of deletion that demonstrated diminished expression in primary melanomas relative to benign nevi and were significantly increased in expression by 5-Aza treatment, and these genes demonstrated growth-suppressive properties with transfection into melanoma-derived cell lines.
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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