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
BRAF, NRAS and HRAS mutations in spitzoid tumours and their possible pathogenetic significance.
TL;DR: The relationships between so‐called spitzoid tumours have proven difficult to understand and new approaches are needed to understand the role of ‘cell reprograming’.
Journal ArticleDOI
Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity.
Felicity Newell,James S. Wilmott,Peter Johansson,Katia Nones,Venkateswar Addala,Venkateswar Addala,Pamela Mukhopadhyay,Natasa Broit,Natasa Broit,Carol M. Amato,Robert Van Gulick,Stephen H. Kazakoff,Ann-Marie Patch,Lambros T. Koufariotis,Vanessa Lakis,Conrad Leonard,Scott Wood,Oliver Holmes,Qinying Xu,Karl D. Lewis,Theresa Medina,Rene Gonzalez,Robyn P. M. Saw,Robyn P. M. Saw,Andrew J. Spillane,Andrew J. Spillane,Jonathan R. Stretch,Jonathan R. Stretch,Robert V. Rawson,Peter M. Ferguson,Tristan J. Dodds,John F. Thompson,John F. Thompson,Georgina V. Long,Georgina V. Long,Mitchell P. Levesque,William A. Robinson,John V. Pearson,Graham J. Mann,Graham J. Mann,Richard A. Scolyer,Nicola Waddell,Nicola Waddell,Nicholas K. Hayward +43 more
TL;DR: In this article, the authors performed whole-genome sequencing of 87 melanoma tumors with matching transcriptome sequencing for 63 tumors and reported that mutational signature analysis revealed a subset of tumors, mostly subungual, with an ultraviolet radiation signature.
Journal ArticleDOI
Nevus density and melanoma risk in women: A pooled analysis to test the divergent pathway hypothesis
Catherine M. Olsen,Michael S. Zens,Therese A. Stukel,Therese A. Stukel,Carlotta Sacerdote,Yu-Mei Chang,Bruce K. Armstrong,Veronique Bataille,Veronique Bataille,Marianne Berwick,J. Mark Elwood,Elizabeth A. Holly,Connie Kirkpatrick,Thomas M. Mack,Julia A. Newton Bishop,Anne Østerlind,Anthony J. Swerdlow,Roberto Zanetti,Adèle C. Green,Margaret R. Karagas,David C. Whiteman +20 more
TL;DR: Aggregate data from 10 case–control studies of melanoma in women suggest that high nevus counts are strongly associated with melanoma of the trunk but less so if at all of the head and neck, which supports different etiologic pathways of melanomas development by anatomic site.
Journal ArticleDOI
miR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy
Animesh Bhattacharya,Ulf Schmitz,Yvonne Raatz,Madeleine Schönherr,Tina Kottek,Marianne Schauer,Sandra Franz,Anja Saalbach,Ulf Anderegg,Olaf Wolkenhauer,Dirk Schadendorf,Jan C. Simon,Thomas M. Magin,Julio Vera,Manfred Kunz +14 more
TL;DR: Taken together, miR-638 supports melanoma progression and suppresses p53-mediated apoptosis pathways, autophagy and expression of the transcriptional repressor TFAP2A/AP-2α.
Journal ArticleDOI
Effects of BRAF Mutations and BRAF Inhibition on Immune Responses to Melanoma
Kristina M. Ilieva,Isabel Correa,Debra H. Josephs,Panagiotis Karagiannis,Isioma U. Egbuniwe,Michiala J. Cafferkey,James Spicer,Mark Harries,Frank O. Nestle,Katie E. Lacy,Sophia N. Karagiannis +10 more
TL;DR: Simultaneous BRAF and MEK inhibition, and especially combination of BRAF inhibitors with new immunotherapies such as checkpoint blockade antibodies, may further enhance immune activation, or counteract immunosuppressive signals.
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%.
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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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