Conjunctival Melanomas Harbor BRAF and NRAS Mutations and Copy Number Changes Similar to Cutaneous and Mucosal Melanomas
Klaus G. Griewank,Henrike Westekemper,Rajmohan Murali,Monika Mach,Bastian Schilling,Thomas Wiesner,Tobias Schimming,Elisabeth Livingstone,Antje Sucker,Florian Grabellus,Claudia H D Metz,Daniela Süsskind,Uwe Hillen,Michael R. Speicher,Scott E. Woodman,Klaus-Peter Steuhl,Dirk Schadendorf +16 more
Reads0
Chats0
TLDR
The presence of NRAS or BRAF mutations in a mutually exclusive pattern in roughly half (47%) of conjunctival melanomas and the pattern of CNAs argue for conjunctive melanoma being closely related to cutaneous and mucosal melanoma but entirely distinct from uveal melanoma.Abstract:
Purpose: Conjunctival melanoma is a rare but potentially deadly tumor of the eye. Despite effective local therapies, recurrence and metastasis remain frequent. Once the tumor has metastasized, treatment options are limited and the prognosis is poor. To date, little is known of the genetic alterations in conjunctival melanomas. Experimental Design: We conducted genetic analysis of 78 conjunctival melanomas, to our knowledge the largest cohort reported to date. An oncogene hotspot array was run on 38 samples, screening for a panel of known cancer-relevant mutations. Thirty tumors were analyzed for genome-wide copy number alterations (CNA) using array-based comparative genomic hybridization. Sanger sequencing of selected target mutations was conducted in all samples. Results: BRAF mutations were identified in 23 of 78 (29%) tumors. NRAS mutations, previously not recognized as relevant in conjunctival melanoma, were detected in 14 of 78 (18%) tumors. We found CNAs affecting various chromosomes distributed across the genome in a pattern reminiscent of cutaneous and mucosal melanoma but differing markedly from uveal melanoma. Conclusions: The presence of NRAS or BRAF mutations in a mutually exclusive pattern in roughly half (47%) of conjunctival melanomas and the pattern of CNAs argue for conjunctival melanoma being closely related to cutaneous and mucosal melanoma but entirely distinct from uveal melanoma. Patients with metastatic conjunctival melanoma should be considered for therapeutic modalities available for metastatic cutaneous and mucosal melanoma including clinical trials of novel agents. Clin Cancer Res; 19(12); 3143–52. ©2013 AACR .read more
Citations
More filters
Journal ArticleDOI
CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic Indications and Ophthalmic Side Effects.
TL;DR: In this paper, a literature review was performed using a PubMed search for publications between 1990 and 2017 to review immune checkpoint inhibitor indications and ophthalmic side effects, using three ligand-specific inhibitors.
Journal ArticleDOI
TERT Promoter Mutation Status as an Independent Prognostic Factor in Cutaneous Melanoma
Klaus G. Griewank,Rajmohan Murali,Joan Anton Puig-Butille,Bastian Schilling,Elisabeth Livingstone,Miriam Potrony,Cristina Carrera,Tobias Schimming,Inga Möller,Marion Schwamborn,Antje Sucker,Uwe Hillen,Celia Badenas,Josep Malvehy,Lisa Zimmer,André Scherag,Susana Puig,Dirk Schadendorf +17 more
TL;DR: UV-induced Tert promoter mutations are one of the most frequent genetic alterations in melanoma, with frequencies varying depending on melanoma subtype, and in nonacral cutaneous melanomas, presence of TERT promoter mutations is independently associated with poor prognosis.
Journal ArticleDOI
Pathways and therapeutic targets in melanoma
Emma Shtivelman,Michael A. Davies,Patrick Hwu,James Chih-Hsin Yang,Michal Lotem,Moshe Oren,Keith T. Flaherty,David E. Fisher +7 more
TL;DR: This review aims to summarize the current knowledge of molecular pathways and their clinical relevance in melanoma and focuses on understanding and overcoming resistance to targeted therapies, and understanding the underlying causes of the heterogeneous responses to immune therapy.
Journal ArticleDOI
Targeted therapy in cancer
TL;DR: The application of discoveries in cancer biology in clinic holds the promise to improve the clinical outcomes in a large scale of patients with cancer and will expedite the development of anticancer drugs and will accelerate the implementation of precision medicine.
Journal ArticleDOI
The biology of uveal melanoma
Adriana Amaro,Rosaria Gangemi,Francesca Piaggio,Giovanna Angelini,Gaia Barisione,Silvano Ferrini,Ulrich Pfeffer +6 more
TL;DR: Current knowledge of the biology of UM is reviewed, several lines of evidence indicate that inflammation and macrophages play a pro-tumor role in UM and in its hepatic metastases, and recent approaches to UM treatment are discussed.
References
More filters
Journal ArticleDOI
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more
TL;DR: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.
Journal ArticleDOI
Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010
Rafael Lozano,Mohsen Naghavi,Kyle J Foreman,Stephen S Lim,Kenji Shibuya,Victor Aboyans,Jerry Abraham,Tim Adair,Rakesh Aggarwal,Stephanie Y. Ahn,Mohammad A. AlMazroa,Miriam Alvarado,H. Ross Anderson,Laurie M. Anderson,Kathryn G. Andrews,Charles Atkinson,Larry M. Baddour,Suzanne Barker-Collo,David Bartels,Michelle L. Bell,Emelia J. Benjamin,Derrick A Bennett,Kavi Bhalla,Boris Bikbov,Aref A. Bin Abdulhak,Gretchen L. Birbeck,Fiona M. Blyth,Ian Bolliger,Soufiane Boufous,Chiara Bucello,Michael Burch,Peter Burney,Jonathan R. Carapetis,Honglei Chen,David Chou,Sumeet S. Chugh,Luc E. Coffeng,Steven D. Colan,Samantha M. Colquhoun,K. Ellicott Colson,John R. Condon,Myles Connor,Myles Connor,Leslie T. Cooper,Matthew A. Corriere,Monica Cortinovis,Karen Courville De Vaccaro,William G. Couser,Benjamin C Cowie,Michael H. Criqui,Marita Cross,Kaustubh Dabhadkar,Nabila Dahodwala,Diego De Leo,Louisa Degenhardt,Allyne Delossantos,Julie O. Denenberg,Don C. Des Jarlais,Samath D Dharmaratne,Samath D Dharmaratne,E. Ray Dorsey,Tim Driscoll,Herbert C. Duber,Beth E. Ebel,Patricia J. Erwin,Patricia Espindola,Majid Ezzati,Valery L. Feigin,Abraham D. Flaxman,Mohammad H. Forouzanfar,F.G.R. Fowkes,Richard C. Franklin,Marlene Fransen,Michael Freeman,Sherine E. Gabriel,Emmanuela Gakidou,Flavio Gaspari,Richard F. Gillum,Diego Gonzalez-Medina,Yara A. Halasa,Diana Haring,James Harrison,Rasmus Havmoeller,Rasmus Havmoeller,Roderick J. Hay,Bruno Hoen,Peter J. Hotez,Damian G Hoy,Kathryn H. Jacobsen,Spencer L. James,Rashmi Jasrasaria,Sudha Jayaraman,Nicole E. Johns,Ganesan Karthikeyan,Nicholas J Kassebaum,Andre Keren,Jon Paul Khoo,Lisa M. Knowlton,Olive Kobusingye,Adofo Koranteng,Rita Krishnamurthi,Michael S Lipnick,Steven E. Lipshultz,Summer Lockett Ohno,Jacqueline Mabweijano,Jacqueline Mabweijano,Michael F. Macintyre,Leslie Mallinger,Lyn March,Guy B. Marks,Robin Marks,Akira Matsumori,Richard Matzopoulos,Richard Matzopoulos,Bongani M. Mayosi,John H. McAnulty,Mary M. McDermott,John J. McGrath,Ziad A. Memish,George A. Mensah,Tony R. Merriman,Catherine Michaud,Matthew J. Miller,Ted R. Miller,Charles Mock,Ana Olga Mocumbi,Ali A. Mokdad,Andrew E. Moran,Kim Mulholland,M. Nathan Nair,Luigi Naldi,K.M. Venkat Narayan,Kiumarss Nasseri,Paul Norman,Martin O'Donnell,Saad B. Omer,Katrina F Ortblad,Richard H. Osborne,Doruk Ozgediz,Bishnu Pahari,Jeyaraj D Pandian,Andrea Panozo Rivero,Rogelio Perez Padilla,Fernando Perez-Ruiz,Norberto Perico,David Phillips,Kelsey Pierce,C. Arden Pope,Esteban Porrini,Farshad Pourmalek,Murugesan Raju,Dharani Ranganathan,Jürgen Rehm,David B. Rein,G. Remuzzi,Frederick P. Rivara,Thomas Roberts,Felipe Rodriguez De Leòn,Lisa C. Rosenfeld,Lesley Rushton,Ralph L. Sacco,Joshua A. Salomon,Uchechukwu Sampson,Ella Sanman,David C. Schwebel,Maria Segui-Gomez,Donald S. Shepard,David Singh,Jessica Singleton,Karen Sliwa,Emma Smith,Andrew C Steer,Jennifer A. Taylor,Bernadette Thomas,Imad M. Tleyjeh,Jeffrey A. Towbin,Thomas Truelsen,Eduardo A. Undurraga,Narayanaswamy Venketasubramanian,Lakshmi Vijayakumar,Theo Vos,Gregory R. Wagner,Mengru Wang,Wenzhi Wang,Kerrianne Watt,Martin A. Weinstock,Robert G. Weintraub,James D. Wilkinson,Anthony D. Woolf,Sarah Wulf,Pon Hsiu Yeh,Paul S. F. Yip,Azadeh Zabetian,Zhi Jie Zheng,Alan D. Lopez,Christopher J L Murray +195 more
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex, using the Cause of Death Ensemble model.
Journal ArticleDOI
Cancer statistics, 2012
TL;DR: The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of about 1,024,400 deaths from cancer, which can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those groups in the lowest socioeconomic bracket.
Journal ArticleDOI
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.
Related Papers (5)
Mutations in GNA11 in Uveal Melanoma
Catherine D. Van Raamsdonk,Klaus G. Griewank,Michelle B. Crosby,Maria C. Garrido,Swapna S. Vemula,Thomas Wiesner,Anna C. Obenauf,Werner Wackernagel,Gary G. R. Green,Nancy Bouvier,M. Mert Sozen,Gail Baimukanova,Ritu Roy,Adriana Heguy,Igor Dolgalev,Raya Khanin,Klaus J. Busam,Michael R. Speicher,Joan M. O'Brien,Boris C. Bastian +19 more