title: Discovery of structural alterations in solid tumor oligodendroglioma by single molecule analysis.
abstract: BACKGROUND
  Solid tumors present a panoply of genomic alterations, from single base changes to the gain or loss of entire chromosomes. Although aberrations at the two extremes of this spectrum are readily defined, comprehensive discernment of the complex and disperse mutational spectrum of cancer genomes remains a significant challenge for current genome analysis platforms. In this context, high throughput, single molecule platforms like Optical Mapping offer a unique perspective.
  
  
  RESULTS
  Using measurements from large ensembles of individual DNA molecules, we have discovered genomic structural alterations in the solid tumor oligodendroglioma. Over a thousand structural variants were identified in each tumor sample, without any prior hypotheses, and often in genomic regions deemed intractable by other technologies. These findings were then validated by comprehensive comparisons to variants reported in external and internal databases, and by selected experimental corroborations. Alterations range in size from under 5 kb to hundreds of kilobases, and comprise insertions, deletions, inversions and compound events. Candidate mutations were scored at sub-genic resolution and unambiguously reveal structural details at aberrant loci.
  
  
  CONCLUSIONS
  The Optical Mapping system provides a rich description of the complex genomes of solid tumors, including sequence level aberrations, structural alterations and copy number variants that power generation of functional hypotheses for oligodendroglioma genetics.
authors.affiliation: Department of Chemistry, UW Biotechnology Center, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Mohana
authors.initials: M
authors.lastname: Ray
authors.forename: Steve
authors.initials: S
authors.lastname: Goldstein
authors.forename: Shiguo
authors.initials: S
authors.lastname: Zhou
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Potamousis
authors.forename: Deepayan
authors.initials: D
authors.lastname: Sarkar
authors.forename: Michael A
authors.initials: MA
authors.lastname: Newton
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Esterberg
authors.forename: Christina
authors.initials: C
authors.lastname: Kendziorski
authors.forename: Oliver
authors.initials: O
authors.lastname: Bogler
authors.forename: David C
authors.initials: DC
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D023281:Genomics / Q000379:methods*; D006801:Humans; D009154:Mutation; D009837:Oligodendroglioma / Q000235:genetics*; D020161:Physical Chromosome Mapping / Q000379:methods*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results