title: A streamlined method for detecting structural variants in cancer genomes by short read paired-end sequencing.
abstract: Defining the architecture of a specific cancer genome, including its structural variants, is essential for understanding tumor biology, mechanisms of oncogenesis, and for designing effective personalized therapies. Short read paired-end sequencing is currently the most sensitive method for detecting somatic mutations that arise during tumor development. However, mapping structural variants using this method leads to a large number of false positive calls, mostly due to the repetitive nature of the genome and the difficulty of assigning correct mapping positions to short reads. This study describes a method to efficiently identify large tumor-specific deletions, inversions, duplications and translocations from low coverage data using SVDetect or BreakDancer software and a set of novel filtering procedures designed to reduce false positive calls. Applying our method to a spontaneous T cell lymphoma arising in a core RAG2/p53-deficient mouse, we identified 40 validated tumor-specific structural rearrangements supported by as few as 2 independent read pairs.
authors.affiliation: Department of Pathology and Laboratory Medicine and Abramson Family Cancer Research Institute, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Martina
authors.initials: M
authors.lastname: Mijušković
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Brown
authors.forename: Zuojian
authors.initials: Z
authors.lastname: Tang
authors.forename: Cory R
authors.initials: CR
authors.lastname: Lindsay
authors.forename: Efstratios
authors.initials: E
authors.lastname: Efstathiadis
authors.forename: Ludovic
authors.initials: L
authors.lastname: Deriano
authors.forename: David B
authors.initials: DB
authors.lastname: Roth
mesh_terms: D000818:Animals; D002869:Chromosome Aberrations; D002874:Chromosome Mapping / Q000379:methods; D019295:Computational Biology / Q000379:methods; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D016678:Genome / Q000235:genetics; D023281:Genomics / Q000379:methods*; D006801:Humans; D016399:Lymphoma, T-Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D016159:Tumor Suppressor Protein p53