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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p38 phosphorylates Rb on Ser567 by a novel, cell cycle-independent mechanism that triggers Rb-Hdm2 interaction and apoptosis.
TL;DR: These findings provide a mechanistic explanation as to how Rb regulates cell division and apoptosis through different kinases, and reveal how Hdm2 may functionally link the tumor suppressors Rb and p53.
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A caveolin-dependent and PI3K/AKT-independent role of PTEN in β-catenin transcriptional activity
Alejandro Conde-Perez,Gwendoline Gros,Christine Longvert,Malin Pedersen,Valérie Petit,Zackie Aktary,Amaya Viros,Franck Gesbert,Véronique Delmas,Florian Rambow,Boris C. Bastian,Andrew D. Campbell,Sophie Colombo,Isabel Puig,Alfonso Bellacosa,Owen J. Sansom,Richard Marais,Léon C van Kempen,Léon C van Kempen,Léon C van Kempen,Lionel Larue +20 more
TL;DR: A mechanism by which loss of PTEN increases CAV1-mediated dissociation of β-catenin from membranous E-cadherin, which may promote senescence bypass and metastasis is revealed.
Journal ArticleDOI
Targeted next generation sequencing reveals unique mutation profile of primary melanocytic tumors of the central nervous system
Johannes van de Nes,Marco Gessi,Antje Sucker,Inga Möller,Mathias Stiller,Susanne Horn,Simone L. Scholz,Carina Pischler,Nadine Stadtler,Bastian Schilling,Lisa Zimmer,Uwe Hillen,Richard A. Scolyer,Michael E. Buckland,Michael E. Buckland,Libero Lauriola,Torsten Pietsch,Andreas Waha,Dirk Schadendorf,Rajmohan Murali,Klaus G. Griewank +20 more
TL;DR: It is shown that while MT-CNS do have GNAQ or GNA11 mutations, they rarely harbor other recurrent mutations found in uveal or cutaneous melanomas.
Journal ArticleDOI
Treatment of cutaneous melanoma: current approaches and future prospects
TL;DR: Emerging data from clinical trials suggest that substantial improvements in the standard of care for melanoma may be possible, and identification of activating mutations of BRAF, NRAS, c-KIT, and GNAQ in distinct clinical subtypes of melanoma suggest that these are molecularly distinct.
Journal ArticleDOI
Revisiting the photochemistry of solar UVA in human skin.
TL;DR: The role of oxidative damage in DNA has been considered paramount in UVA carcinogenesis and UVA-associated pathologies, leading to a re-evaluation of the importance of UVA in human health and its mechanism of action on human tissues.
References
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Mutations of the BRAF gene in human cancer
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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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