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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The genomic landscape of childhood and adolescent melanoma.
Charles Lu,Jinghui Zhang,Panduka Nagahawatte,John Easton,Seungjae Lee,Zhifa Liu,Li Ding,Matthew A. Wyczalkowski,Marcus B. Valentine,Fariba Navid,Heather L. Mulder,Ruth G. Tatevossian,James Dalton,James Davenport,Zhirong Yin,Michael N. Edmonson,Michael Rusch,Gang Wu,Yongjin Li,Matthew Parker,Erin Hedlund,Sheila A. Shurtleff,Susana C. Raimondi,Vadodaria Bhavin,Yergeau Donald,Elaine R. Mardis,Richard K. Wilson,William E. Evans,David W. Ellison,Stanley Pounds,Michael A. Dyer,James R. Downing,Alberto S. Pappo,Armita Bahrami +33 more
TL;DR: It is concluded that pediatric CM has a very similar UV-induced mutational spectrum to that found in the adult counterpart, emphasizing the need to promote sun protection practices in early life and to improve access to therapeutic agents being explored in adults in young patients.
Journal ArticleDOI
Predictors of Survival in Mucosal Melanoma of the Head and Neck
TL;DR: In this large cohort of patients with MMHN, several novel factors robustly predictive of overall and melanoma-specific survival are identified.
Journal ArticleDOI
Oncogene-directed alterations in cancer cell metabolism.
TL;DR: Evidence for oncogene-directed cancer metabolic regulation is presented and the importance of identifying underlying mechanisms that can be targeted for developing precision cancer therapies is discussed.
Journal ArticleDOI
Ipilimumab for Patients With Advanced Mucosal Melanoma
Michael A. Postow,Jason J. Luke,Mark J. Bluth,Nikhil H. Ramaiya,Katherine S. Panageas,Donald P. Lawrence,Nageatte Ibrahim,Keith T. Flaherty,Ryan J. Sullivan,Patrick A. Ott,Margaret K. Callahan,James J. Harding,Sandra P. D'Angelo,Mark A. Dickson,Gary K. Schwartz,Paul B. Chapman,Sacha Gnjatic,Sacha Gnjatic,Jedd D. Wolchok,F. Stephen Hodi,Richard D. Carvajal +20 more
TL;DR: A multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab found several patients demonstrated serologic responses to cancer-testis antigens and other antIGens, but the overall response rate was low.
Journal ArticleDOI
Evolving concepts in melanoma classification and their relevance to multidisciplinary melanoma patient care
TL;DR: In the initial period after melanoma was recognised as a disease entity in the early 1800's, it was subclassified on the basis of its presumed origin, but recently, mutually exclusive oncogenic mutations in melanomas involving NRAS, BRAF, CKIT, and GNAQ/GNA11 have been identified and might herald the beginning of a new molecular classification of melanoma.
References
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Journal ArticleDOI
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%.
Journal ArticleDOI
R: A Language for Data Analysis and Graphics
Ross Ihaka,Robert Gentleman +1 more
TL;DR: In this article, the authors discuss their experience designing and implementing a statistical computing language, which combines what they felt were useful features from two existing computer languages, and they feel that the new language provides advantages in the areas of portability, computational efficiency, memory management, and scope.
Journal ArticleDOI
A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4
TL;DR: P16 seems to act in a regulatory feedback circuit with CDK4, D-type cyclins and retinoblastoma protein, and inhibits the catalytic activity of theCDK4/cyclin D enzymes.
Journal ArticleDOI
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.
Journal ArticleDOI
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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