title: Clinicopathological features and clinical outcomes associated with TP53 and BRAFNon-V600mutations in cutaneous melanoma patients.
abstract: BRAFV600, NRAS, TP53, and BRAFNon-V600are among the most common mutations detected in non-acral cutaneous melanoma patients. Although several studies have identified clinical and pathological features associated with BRAFV600and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BRAFNon-V600mutations.
  
  
  
  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).
  
  
  
  The prevalence of BRAFV600, NRAS, TP53, and BRAFNon-V600mutations 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-V600mutations were associated with older age (P = .005) but not with primary tumor features or OS from stage IV. Neither TP53 nor BRAFNon-V600mutations 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-V600mutations 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.
  
  
  
  These results add to the understanding of the clinical features associated with TP53 and BRAFNon-V600mutations 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. © 2016 American Cancer Society.
authors.affiliation: Department of Medical Oncology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Haydu
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Aron Y
authors.initials: AY
authors.lastname: Joon
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Roland L
authors.initials: RL
authors.lastname: Bassett
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Alan E
authors.initials: AE
authors.lastname: Siroy
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tetzlaff
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Routbort
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rodabe N
authors.initials: RN
authors.lastname: Amaria
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Wargo
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: McQuade
authors.affiliation: Department of Internal Medicine, Baylor College of Medicine, Houston, Texas.
authors.forename: Jan
authors.initials: J
authors.lastname: Kemnade
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Woodman
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jason
authors.initials: J
authors.lastname: Roszik
authors.affiliation: Melanoma Clinical Research Program, California Pacific Medical Center, San Francisco, California.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Kim
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Gershenwald
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Lazar
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Davies
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D059645:Mutation Rate; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult; D000096142:Cutaneous Malignant Melanoma
chemical_list: D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D016159:Tumor Suppressor Protein p53; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAFNon-V600; BRAFV600; TP53; melanoma; mutations