title: Comparative exome sequencing of metastatic lesions provides insights into the mutational progression of melanoma.
abstract: BACKGROUND
  Metastasis is characterized by spreading of neoplastic cells to an organ other than where they originated and is the predominant cause of death among cancer patients. This holds true for melanoma, whose incidence is increasing more rapidly than any other cancer and once disseminated has few therapeutic options. Here we performed whole exome sequencing of two sets of matched normal and metastatic tumor DNAs.
  
  
  RESULTS
  Using stringent criteria, we evaluated the similarities and differences between the lesions. We find that in both cases, 96% of the single nucleotide variants are shared between the two metastases indicating that clonal populations gave rise to the distant metastases. Analysis of copy number variation patterns of both metastatic sets revealed a trend similar to that seen with our single nucleotide variants. Analysis of pathway enrichment on tumor sets shows commonly mutated pathways enriched between individual sets of metastases and all metastases combined.
  
  
  CONCLUSIONS
  These data provide a proof-of-concept suggesting that individual metastases may have sufficient similarity for successful targeting of driver mutations.
authors.affiliation: The Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Gartner
authors.forename: Sean
authors.initials: S
authors.lastname: Davis
authors.forename: Xiaomu
authors.initials: X
authors.lastname: Wei
authors.forename: Jimmy C
authors.initials: JC
authors.lastname: Lin
authors.forename: Niraj S
authors.initials: NS
authors.lastname: Trivedi
authors.forename: Jamie K
authors.initials: JK
authors.lastname: Teer
authors.forename: Paul S
authors.initials: PS
authors.lastname: Meltzer
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Yardena
authors.initials: Y
authors.lastname: Samuels
mesh_terms: D045744:Cell Line, Tumor; D004247:DNA / Q000032:analysis*; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D004247:DNA