Dae Won Kim1, Lauren E Haydu2, Aron Y Joon3, Roland L Bassett3, Alan E Siroy4, Michael T Tetzlaff4,5, Mark J Routbort4, Rodabe N Amaria6, Jennifer A Wargo2,7, Jennifer L McQuade6, Jan Kemnade8, Patrick Hwu6, Scott E Woodman6,9, Jason Roszik6,9, Kevin B Kim10, Jeffrey E Gershenwald2,11, Alexander J Lazar4,5, Michael A Davies5,6,9. 1. Department of Medical Oncology, Moffitt Cancer Center, Tampa, Florida. 2. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 3. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas. 4. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 5. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 6. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 7. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. 8. Department of Internal Medicine, Baylor College of Medicine, Houston, Texas. 9. Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 10. Melanoma Clinical Research Program, California Pacific Medical Center, San Francisco, California. 11. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Abstract
BACKGROUND: BRAFV600 , NRAS, TP53, and BRAFNon-V600 are among the most common mutations detected in non-acral cutaneous melanoma patients. Although several studies have identified clinical and pathological features associated with BRAFV600 and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BRAFNon-V600 mutations. METHODS: This study analyzed the patient demographics, primary tumor features, and clinical outcomes of a large cohort of non-acral cutaneous melanoma patients who had undergone clinically indicated molecular testing (n = 926). RESULTS: The prevalence of BRAFV600 , NRAS, TP53, and BRAFNon-V600 mutations was 43%, 21%, 19%, and 7%, respectively. The presence of a TP53 mutation was associated with older age (P = .019), a head and neck primary tumor site (P = .0001), and longer overall survival (OS) from the diagnosis of stage IV disease in univariate (P = .039) and multivariate analyses (P = .015). BRAFNon-V600 mutations were associated with older age (P = .005) but not with primary tumor features or OS from stage IV. Neither TP53 nor BRAFNon-V600 mutations correlated significantly with OS with frontline ipilimumab treatment, and the TP53 status was not significantly associated with outcomes with frontline BRAF inhibitor therapy. Eleven patients with BRAFNon-V600 mutations were treated with a BRAF inhibitor. Three patients were not evaluable for a response because of treatment cessation for toxicities; the remaining patients had disease progression as the best response to therapy. CONCLUSIONS: These results add to the understanding of the clinical features associated with TP53 and BRAFNon-V600 mutations in advanced cutaneous melanoma patients, and they support the rationale for evaluating the prognostic significance of TP53 in other cohorts of melanoma patients. Cancer 2017;123:1372-1381.
BACKGROUND: BRAFV600 , NRAS, TP53, and BRAFNon-V600 are among the most common mutations detected in non-acral cutaneous melanomapatients. Although several studies have identified clinical and pathological features associated with BRAFV600 and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BRAFNon-V600 mutations. METHODS: This study analyzed the patient demographics, primary tumor features, and clinical outcomes of a large cohort of non-acral cutaneous melanomapatients who had undergone clinically indicated molecular testing (n = 926). RESULTS: The prevalence of BRAFV600 , NRAS, TP53, and BRAFNon-V600 mutations was 43%, 21%, 19%, and 7%, respectively. The presence of a TP53 mutation was associated with older age (P = .019), a head and neck primary tumor site (P = .0001), and longer overall survival (OS) from the diagnosis of stage IV disease in univariate (P = .039) and multivariate analyses (P = .015). BRAFNon-V600 mutations were associated with older age (P = .005) but not with primary tumor features or OS from stage IV. Neither TP53 nor BRAFNon-V600 mutations correlated significantly with OS with frontline ipilimumab treatment, and the TP53 status was not significantly associated with outcomes with frontline BRAF inhibitor therapy. Eleven patients with BRAFNon-V600 mutations were treated with a BRAF inhibitor. Three patients were not evaluable for a response because of treatment cessation for toxicities; the remaining patients had disease progression as the best response to therapy. CONCLUSIONS: These results add to the understanding of the clinical features associated with TP53 and BRAFNon-V600 mutations in advanced cutaneous melanomapatients, and they support the rationale for evaluating the prognostic significance of TP53 in other cohorts of melanomapatients. Cancer 2017;123:1372-1381.
Authors: John A Jakob; Roland L Bassett; Chaan S Ng; Jonathan L Curry; Richard W Joseph; Gladys C Alvarado; Michelle L Rohlfs; Jessie Richard; Jeffrey E Gershenwald; Kevin B Kim; Alexander J Lazar; Patrick Hwu; Michael A Davies Journal: Cancer Date: 2011-12-16 Impact factor: 6.860
Authors: Tamara Terzian; Enrique C Torchia; Daisy Dai; Steven E Robinson; Kazutoshi Murao; Regan A Stiegmann; Victoria Gonzalez; Glen M Boyle; Marianne B Powell; Pamela M Pollock; Guillermina Lozano; William A Robinson; Dennis R Roop; Neil F Box Journal: Pigment Cell Melanoma Res Date: 2010-12 Impact factor: 4.693
Authors: David S Hong; Luis Vence; Gerald Falchook; Laszlo G Radvanyi; Chengwen Liu; Vicki Goodman; Jeffery J Legos; Sam Blackman; Antonio Scarmadio; Razelle Kurzrock; Gregory Lizee; Patrick Hwu Journal: Clin Cancer Res Date: 2012-02-21 Impact factor: 12.531
Authors: M Luana Poeta; Judith Manola; Meredith A Goldwasser; Arlene Forastiere; Nicole Benoit; Joseph A Califano; John A Ridge; Jarrard Goodwin; Daniel Kenady; John Saunders; William Westra; David Sidransky; Wayne M Koch Journal: N Engl J Med Date: 2007-12-20 Impact factor: 91.245
Authors: Kimberly Brown Dahlman; Junfeng Xia; Katherine Hutchinson; Charles Ng; Donald Hucks; Peilin Jia; Mohammad Atefi; Zengliu Su; Suzanne Branch; Pamela L Lyle; Donna J Hicks; Viviana Bozon; John A Glaspy; Neal Rosen; David B Solit; James L Netterville; Cindy L Vnencak-Jones; Jeffrey A Sosman; Antoni Ribas; Zhongming Zhao; William Pao Journal: Cancer Discov Date: 2012-07-13 Impact factor: 39.397
Authors: Amaya Viros; Berta Sanchez-Laorden; Malin Pedersen; Simon J Furney; Joel Rae; Kate Hogan; Sarah Ejiama; Maria Romina Girotti; Martin Cook; Nathalie Dhomen; Richard Marais Journal: Nature Date: 2014-06-11 Impact factor: 49.962
Authors: Bradley Garman; Ioannis N Anastopoulos; Clemens Krepler; Patricia Brafford; Katrin Sproesser; Yuchao Jiang; Bradley Wubbenhorst; Ravi Amaravadi; Joseph Bennett; Marilda Beqiri; David Elder; Keith T Flaherty; Dennie T Frederick; Tara C Gangadhar; Michael Guarino; David Hoon; Giorgos Karakousis; Qin Liu; Nandita Mitra; Nicholas J Petrelli; Lynn Schuchter; Batool Shannan; Carol L Shields; Jennifer Wargo; Brandon Wenz; Melissa A Wilson; Min Xiao; Wei Xu; Xaiowei Xu; Xiangfan Yin; Nancy R Zhang; Michael A Davies; Meenhard Herlyn; Katherine L Nathanson Journal: Cell Rep Date: 2017-11-14 Impact factor: 9.423
Authors: Yibing Yan; Matthew J Wongchenko; Caroline Robert; James Larkin; Paolo A Ascierto; Brigitte Dréno; Michele Maio; Claus Garbe; Paul B Chapman; Jeffrey A Sosman; Zhen Shi; Hartmut Koeppen; Jessie J Hsu; Ilsung Chang; Ivor Caro; Isabelle Rooney; Grant A McArthur; Antoni Ribas Journal: Clin Cancer Res Date: 2019-03-01 Impact factor: 12.531
Authors: Nathaniel J Myall; Solomon Henry; Douglas Wood; Joel W Neal; Summer S Han; Sukhmani K Padda; Heather A Wakelee Journal: Clin Lung Cancer Date: 2018-10-23 Impact factor: 4.785
Authors: Caroline A Nebhan; Douglas B Johnson; Ryan J Sullivan; Roda N Amaria; Keith T Flaherty; Jeffrey A Sosman; Michael A Davies Journal: Oncologist Date: 2021-05-04 Impact factor: 5.837
Authors: Charlotte Welinder; Krzysztof Pawłowski; A Marcell Szasz; Maria Yakovleva; Yutaka Sugihara; Johan Malm; Göran Jönsson; Christian Ingvar; Lotta Lundgren; Bo Baldetorp; Håkan Olsson; Melinda Rezeli; Thomas Laurell; Elisabet Wieslander; György Marko-Varga Journal: PLoS One Date: 2017-04-26 Impact factor: 3.240
Authors: Eszter Molnár; Dominika Rittler; Marcell Baranyi; Michael Grusch; Walter Berger; Balázs Döme; József Tóvári; Clemens Aigner; József Tímár; Tamás Garay; Balázs Hegedűs Journal: BMC Cancer Date: 2018-05-08 Impact factor: 4.430
Authors: Antonio G Richetta; Virginia Valentini; Federica Marraffa; Giovanni Paolino; Piera Rizzolo; Valentina Silvestri; Veronica Zelli; Anna Carbone; Cinzia Di Mattia; Stefano Calvieri; Pasquale Frascione; Pietro Donati; Laura Ottini Journal: Oncotarget Date: 2018-08-14
Authors: Thomas T DeLeon; Daniel R Almquist; Benjamin R Kipp; Blake T Langlais; Aaron Mangold; Jennifer L Winters; Heidi E Kosiorek; Richard W Joseph; Roxana S Dronca; Matthew S Block; Robert R McWilliams; Lisa A Kottschade; Kandelaria M Rumilla; Jesse S Voss; Mahesh Seetharam; Aleksandar Sekulic; Svetomir N Markovic; Alan H Bryce Journal: PLoS One Date: 2020-03-20 Impact factor: 3.240