title: Somatic and germline analyses of a long term melanoma survivor with a recurrent brain metastasis.
abstract: BACKGROUND
  Median overall survival (OS) of patients with melanoma brain metastases (MBM) is usually 6 months or less. There are rare reports of patients with treated MBM who survived for years. These outlier cases represent valuable opportunities to study the somatic and germline factors that may have influenced patient outcome and led to extended survival.
  
  
  METHODS
  Here we report the clinical scenario of a 67 year old man with a recurrent brain metastasis from melanoma who has survived over 12 years post-resection. We review the literature relating to clinical and molecular variables associated with long term survival post-brain metastasis. We present the somatic characteristics of this individual patient's tumor as well as an analysis of inherited genetic variants related to immune function. The patient's resected brain tumor is BRAF V600E mutated, NRAS wild type (WT), and TERT C250T mutated. The patient is a carrier of germline variants in immunomodulatory loci associated with prolonged survival.
  
  
  CONCLUSIONS
  Our data suggest that genetic variants in immunomodulatory loci may partially contribute to this patient's unusually favorable outcome and should not be overlooked. With further and future investigation, knowledge of inherited single nucleotide polymorphisms (SNPs) may provide clinicians with more individualized prognostic information for melanoma patients, with potential implications for surveillance strategies and therapeutic interventions.
authors.affiliation: Deparment of Medicine, New York University School of Medicine, 522 First Ave., Smilow Building Room 403, New York, NY, 10016, USA. Sarah.Weiss@nyumc.org.|Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, 522 First Ave., Smilow 403, New York, NY, 10016, USA. Sarah.Weiss@nyumc.org.
authors.forename: Sarah
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, 522 First Ave., Smilow 403, New York, NY, 10016, USA. Farbod.Darvishian@nyumc.org.|Department of Pathology, New York University School of Medicine, 540-562 First Ave., New York, NY, 10016, USA. Farbod.Darvishian@nyumc.org.
authors.forename: Farbod
authors.initials: F
authors.lastname: Darvishian
authors.affiliation: The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, 522 First Ave., Smilow 4th floor, New York, NY, 10016, USA. Jyothi.Tadepalli@nyumc.org.
authors.forename: Jyothi
authors.initials: J
authors.lastname: Tadepalli
authors.affiliation: Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, 522 First Ave., Smilow 403, New York, NY, 10016, USA. Richard.Shapiro@nyumc.org.|Department of Surgery, New York University School of Medicine, 160 E. 34th St., 4th floor, New York, NY, 10016, USA. Richard.Shapiro@nyumc.org.
authors.forename: Richard
authors.initials: R
authors.lastname: Shapiro
authors.affiliation: Department of Neurosurgery, New York University School of Medicine, 530 First Ave., 8th floor, New York, NY, 10016, USA. John.Golfinos@nyumc.org.
authors.forename: John
authors.initials: J
authors.lastname: Golfinos
authors.affiliation: Deparment of Medicine, New York University School of Medicine, 522 First Ave., Smilow Building Room 403, New York, NY, 10016, USA. Anna.Pavlick@nyumc.org.|Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, 522 First Ave., Smilow 403, New York, NY, 10016, USA. Anna.Pavlick@nyumc.org.
authors.forename: Anna
authors.initials: A
authors.lastname: Pavlick
authors.affiliation: Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, 522 First Ave., Smilow 403, New York, NY, 10016, USA. David.Polsky@nyumc.org.|The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, 522 First Ave., Smilow 4th floor, New York, NY, 10016, USA. David.Polsky@nyumc.org.
authors.forename: David
authors.initials: D
authors.lastname: Polsky
authors.affiliation: Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, 522 First Ave., Smilow 403, New York, NY, 10016, USA. Tomas.Kirchhoff@nyumc.org.|Departments of Population Health and Environmental Medicine, New York University School of Medicine, 522 First Ave., Smilow 12th floor, New York, NY, 10016, USA. Tomas.Kirchhoff@nyumc.org.
authors.forename: Tomas
authors.initials: T
authors.lastname: Kirchhoff
authors.affiliation: Deparment of Medicine, New York University School of Medicine, 522 First Ave., Smilow Building Room 403, New York, NY, 10016, USA. Iman.Osman@nyumc.org.|Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, 522 First Ave., Smilow 403, New York, NY, 10016, USA. Iman.Osman@nyumc.org.|The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, 522 First Ave., Smilow 4th floor, New York, NY, 10016, USA. Iman.Osman@nyumc.org.
authors.forename: Iman
authors.initials: I
authors.lastname: Osman
mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D020558:GTP Phosphohydrolases / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D017741:Survivors; D019098:Telomerase / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human