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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Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation
Paul B. Chapman,Axel Hauschild,Caroline Robert,John B. A. G. Haanen,Paolo A. Ascierto,James Larkin,Reinhard Dummer,Claus Garbe,Alessandro Testori,Michele Maio,David W. Hogg,Paul Lorigan,Céleste Lebbé,Thomas Jouary,Dirk Schadendorf,Antoni Ribas,Jeffrey A. Sosman,John M. Kirkwood,Brigitte Dréno,K. B. Nolop,Jiang Li,B. Nelson,Jeannie Hou,Richard J. Lee,Keith T. Flaherty,Grant A. McArthur +25 more
TL;DR: Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation in a phase 3 randomized clinical trial.
Journal ArticleDOI
The future of immune checkpoint therapy
Padmanee Sharma,James P. Allison +1 more
TL;DR: The way forward for this class of novel agents lies in the ability to understand human immune responses in the tumor microenvironment, which will provide valuable information regarding the dynamic nature of the immune response and regulation of additional pathways that will need to be targeted through combination therapies to provide survival benefit for greater numbers of patients.
Journal ArticleDOI
Inhibition of mutated, activated BRAF in metastatic melanoma.
Keith T. Flaherty,Igor Puzanov,Kevin B. Kim,Antoni Ribas,Grant A. McArthur,Jeffrey A. Sosman,Peter J. O'Dwyer,Richard J. Lee,Joseph F. Grippo,K. B. Nolop,Paul B. Chapman +10 more
TL;DR: Treatment of metastatic melanoma with PLX4032 in patients with tumors that carry the V600E BRAF mutation resulted in complete or partial tumor regression in the majority of patients.
Journal ArticleDOI
Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial
Axel Hauschild,Jean-Jacques Grob,Lev V. Demidov,Thomas Jouary,Ralf Gutzmer,Michael Millward,Piotr Rutkowski,Christian U. Blank,Wilson H. Miller,Eckhart Kaempgen,Salvador Martín-Algarra,Boguslawa Karaszewska,Cornelia Mauch,Vanna Chiarion-Sileni,Anne-Marie Martin,Suzanne Swann,Patricia Haney,Beloo Mirakhur,Mary E. Guckert,Vicki L. Goodman,Paul B. Chapman +20 more
TL;DR: Dabrafenib significantly improved progression-free survival compared with dacarbazine, and skin-related toxic effects, fever, fatigue, arthralgia, and headache were uncommon in both groups.
Journal ArticleDOI
Genomic Classification of Cutaneous Melanoma
Rehan Akbani,Kadir C. Akdemir,B. Arman Aksoy,Monique Albert,Adrian Ally,Samirkumar B. Amin,Harindra Arachchi,Arshi Arora,J. Todd Auman,Brenda Ayala,Julien Baboud,Miruna Balasundaram,Saianand Balu,Nandita Barnabas,John M. S. Bartlett,Pam Bartlett,Boris C. Bastian,Stephen B. Baylin,Madhusmita Behera,Dmitry Belyaev,Christopher C. Benz,Brady Bernard,Rameen Beroukhim,Natalie Bir,Aaron D. Black,Tom Bodenheimer,Lori Boice,Genevieve M. Boland,Riccardo Bono,Moiz S. Bootwalla,Marcus Bosenberg,Jay Bowen,Reanne Bowlby,Christopher A. Bristow,Laura Brockway-Lunardi,Denise Brooks,Jakub Brzezinski,Wiam Bshara,Elizabeth Buda,William R. Burns,Yaron S.N. Butterfield,Michael Button,Tiffany L. Calderone,Giancarlo Antonini Cappellini,Candace D. Carter,Scott L. Carter,Lynn Cherney,Andrew D. Cherniack,Aaron Chevalier,Lynda Chin,Juok Cho,Raymond J. Cho,Yoon La Choi,Andy Chu,Sudha Chudamani,Kristian Cibulskis,Giovanni Ciriello,Amanda Clarke,Stephen Coons,Leslie Cope,Daniel Crain,Erin Curley,Ludmila Danilova,Stefania D'Atri,Tanja Davidsen,Michael A. Davies,Keith A. Delman,John A. Demchok,Qixia A. Deng,Yonathan Lissanu Deribe,Noreen Dhalla,Rajiv Dhir,Daniel DiCara,Michael Dinikin,Michael Dubina,J. Stephen Ebrom,Sophie Egea,Greg Eley,Jay Engel,Jennifer Eschbacher,Konstantin V. Fedosenko,Ina Felau,Timothy R. Fennell,Martin L. Ferguson,Sheila Fisher,Keith T. Flaherty,Scott Frazer,Jessica Frick,Victoria Fulidou,Stacey Gabriel,Jianjiong Gao,Johanna Gardner,Levi A. Garraway,Julie M. Gastier-Foster,Carmelo Gaudioso,Nils Gehlenborg,Giannicola Genovese,Mark Gerken,Jeffrey E. Gershenwald,Gad Getz,Carmen Gomez-Fernandez,Thomas Gribbin,Jonna Grimsby,Benjamin Gross,Ranabir Guin,Tony Gutschner,Angela Hadjipanayis,Ruth Halaban,Benjamin Hanf,David Haussler,Lauren E. Haydu,D. Neil Hayes,Nicholas K. Hayward,David I. Heiman,Lynn M. Herbert,James G. Herman,Peter Hersey,Katherine A. Hoadley,Eran Hodis,Robert A. Holt,Dave S.B. Hoon,Susan Hoppough,Alan P. Hoyle,Franklin W. Huang,Mei Huang,Sharon K. Huang,Carolyn M. Hutter,Matthew Ibbs,Lisa Iype,Anders Jacobsen,Valerie Jakrot,Alyssa Janning,William R. Jeck,Stuart R. Jefferys,Mark A. Jensen,Corbin D. Jones,Steven J.M. Jones,Zhenlin Ju,Hojabr Kakavand,Hyojin Kang,Richard F. Kefford,Fadlo R. Khuri,Jaegil Kim,John M. Kirkwood,Joachim Klode,Anil Korkut,Konstanty Korski,Michael Krauthammer,Raju Kucherlapati,Lawrence N. Kwong,Witold Kycler,Marc Ladanyi,Phillip H. Lai,Peter W. Laird,Eric S. Lander,Michael S. Lawrence,Alexander J. Lazar,Radoslaw Łaźniak,Darlene Lee,Jeffrey E. Lee,Junehawk Lee,Kenneth K. Lee,Semin Lee,William Lee,Ewa Leporowska,Kristen M. Leraas,Haiyan I. Li,Tara M. Lichtenberg,Lee Lichtenstein,Pei Lin,Shiyun Ling,Jia Liu,Ouida Liu,Wen-Bin Liu,Georgina V. Long,Yiling Lu,Singer Ma,Yussanne Ma,Andrzej Mackiewicz,Harshad S. Mahadeshwar,Jared Malke,David Mallery,Georgy Manikhas,Graham J. Mann,Marco A. Marra,Brenna Matejka,Michael Mayo,Sousan Mehrabi,Shaowu Meng,Matthew Meyerson,Piotr A. Mieczkowski,John P. Miller,Martin L. Miller,Gordon B. Mills,Fedor Moiseenko,Richard A. Moore,Scott Morris,Carl Morrison,Donald L. Morton,Stergios J. Moschos,Lisle E. Mose,Florian L. Muller,Andrew J. Mungall,D. Murawa,Pawel Murawa,Bradley A. Murray,Luigi Nezi,Sam Ng,Dana Nicholson,Michael S. Noble,Adeboye Osunkoya,Taofeek K. Owonikoko,Bradley A. Ozenberger,Elena Pagani,Oxana Paklina,Angeliki Pantazi,Michael Parfenov,Jeremy Parfitt,Peter J. Park,Woong-Yang Park,Joel S. Parker,Francesca Passarelli,Robert Penny,Charles M. Perou,Todd Pihl,Olga Potapova,Victor G. Prieto,Alexei Protopopov,Michael J. Quinn,Amie Radenbaugh,Kunal Rai,Suresh Ramalingam,Ayush T. Raman,Nilsa C. Ramirez,Ricardo Ramirez,Uma Rao,W. Kimryn Rathmell,Xiaojia Ren,Sheila Reynolds,Jeffrey Roach,A. Gordon Robertson,Merrick I. Ross,Jason Roszik,Giandomenico Russo,Gordon Saksena,Charles Saller,Yardena Samuels,Chris Sander,Cindy Sander,George E. Sandusky,Netty Santoso,Melissa Saul,Robyn P. M. Saw,Dirk Schadendorf,Jacqueline E. Schein,Nikolaus Schultz,Steven E. Schumacher,Charles Schwallier,Richard A. Scolyer,Jonathan G. Seidman,Pedamallu Chandra Sekhar,Harmanjatinder S. Sekhon,Yasin Senbabaoglu,Sahil Seth,Kerwin F. Shannon,Samantha Sharpe,Norman E. Sharpless,Kenna R. Mills Shaw,Candace Shelton,Troy Shelton,Ronglai Shen,Margi Sheth,Yan Shi,Carolyn J. Shiau,Ilya Shmulevich,Gabriel Sica,Janae V. Simons,Rileen Sinha,Payal Sipahimalani,Heidi J. Sofia,Matthew G. Soloway,Xingzhi Song,Carrie Sougnez,Andrew J. Spillane,Arkadiusz Spychała,Jonathan R. Stretch,Joshua M. Stuart,Wiktoria Maria Suchorska,Antje Sucker,S. Onur Sumer,Yichao Sun,Maria Synott,Barbara Tabak,Teresa R. Tabler,Angela Tam,Donghui Tan,Jiabin Tang,Roy Tarnuzzer,Katherine Tarvin,Honorata Tatka,Barry S. Taylor,M. Teresiak,Nina Thiessen,John F. Thompson,Leigh B. Thorne,Vesteinn Thorsson,Jeffrey M. Trent,Timothy J. Triche,Kenneth Y. Tsai,Peiling Tsou,David Van Den Berg,Eliezer M. Van Allen,Umadevi Veluvolu,Roeland Verhaak,Douglas Voet,Olga Voronina,Vonn Walter,Jessica Walton,Yunhu Wan,Yuling Wang,Zhining Wang,Scot Waring,Ian R. Watson,Nils Weinhold,John N. Weinstein,Daniel J. Weisenberger,Peter White,Matthew D. Wilkerson,James S. Wilmott,Lisa Wise,Maciej Wiznerowicz,Scott E. Woodman,Chang Jiun Wu,Chia Chin Wu,Junyuan Wu,Ye Wu,Ruibin Xi,Andrew Wei Xu,Da Yang,Liming Yang,Lixing Yang,Travis I. Zack,Jean C. Zenklusen,Hailei Zhang,Jianhua Zhang,Wei Zhang,Xiaobei Zhao,Jingchun Zhu,Kelsey Zhu,Lisa Zimmer,Erik Zmuda,Lihua Zou +351 more
TL;DR: This clinicopathological and multi-dimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.
References
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Journal ArticleDOI
Cutaneous melanoma: Prognosis and treatment results worldwide
TL;DR: This first metanalysis of melanoma from treatment centers worldwide consisted of 15,798 patients with localized melanoma (stages I and II) and 2,116 stage II melanoma patients with nodal metastases, and women had a statistically significant survival advantage over men.
Journal ArticleDOI
p53 expression and risk factors for cutaneous melanoma: A case‐control study
TL;DR: The determinants of p53‐positive and p53-negative melanomas were independent and complementary, the former being associated with features of sun‐sensitivity and chronic sun exposure, the latter with phenotypic markers of melanocytic proliferation.
Journal ArticleDOI
The relationship of malignant melanoma, basal and squamous skin cancers to indoor and outdoor work.
Valerie Beral,Nicola Robinson +1 more
TL;DR: An analysis of occupational incidence data for malignant melanomas and squamous-and basal-self carcinomas of the skin in England and Wales from 1970 to 1975 suggests that prolonged occupational exposure to sunlight is an important cause ofSquamous- and basal-cell carcinomas and of melanoma of the head, face and neck, but not of melanomas on other parts of the body.
Journal ArticleDOI
Is there more than one road to melanoma
TL;DR: The study of BRAF gene mutations in 115 patients with invasive primary melanomas found that BRAF mutations were statistically significantly more common in melanomas occurring on intermittently sun-exposed skin than elsewhere, suggesting that distinct genetic pathways lead to melanoma.
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