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
Superior Outcome of Women With Stage I/II Cutaneous Melanoma: Pooled Analysis of Four European Organisation for Research and Treatment of Cancer Phase III Trials
Arjen Joosse,Sandra Collette,Stefan Suciu,Tamar Nijsten,Ferdy Lejeune,Ulrich R. Kleeberg,Jan Willem Coebergh,Alexander M.M. Eggermont,Esther de Vries +8 more
TL;DR: Women have a consistent and independent relative advantage in all aspects of the progression of localized melanoma of approximately 30%, most likely caused by an underlying biologic sex difference.
Journal ArticleDOI
Analysis of the genome to personalize therapy for melanoma
TL;DR: The molecular targets that have been validated clinically, additional genetic events that are candidates for future trials, and the challenges that remain to improve outcomes further in this aggressive disease are discussed.
Journal ArticleDOI
Unraveling the crosstalk between melanoma and immune cells in the tumor microenvironment
TL;DR: An effective therapeutic strategy will require coordinate activation of tumor-specific immunity as well as increased recognition and accessibility of melanoma cells in primary tumors and distal metastases, and methods that have been developed to restore immunity are emphasized.
Journal ArticleDOI
G-quadruplexes: a promising target for cancer therapy.
TL;DR: In this article, a correlation between G4 structure formation and an increased intratumor heterogeneity was identified, which suggests that G4 structures might allow breast cancer stratification and support the identification of new personalized treatment options.
Journal ArticleDOI
Genome sequencing of mucosal melanomas reveals that they are driven by distinct mechanisms from cutaneous melanoma.
Simon J. Furney,Samra Turajlic,Gordon Stamp,Mahrokh Nohadani,Anna Carlisle,J. Meirion Thomas,Andrew J. Hayes,Dirk C. Strauss,Martin Gore,Joost van den Oord,James Larkin,Richard Marais +11 more
TL;DR: The data suggest that different mechanisms underlie the genesis of these diseases and that structural variations play a more important role in mucosal than in cutaneous melanomagenesis, and that mucosal andcutaneous melanomas are distinct diseases with discrete genetic features.
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
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.
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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
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