title: Complex landscapes of somatic rearrangement in human breast cancer genomes.
abstract: Multiple somatic rearrangements are often found in cancer genomes; however, the underlying processes of rearrangement and their contribution to cancer development are poorly characterized. Here we use a paired-end sequencing strategy to identify somatic rearrangements in breast cancer genomes. There are more rearrangements in some breast cancers than previously appreciated. Rearrangements are more frequent over gene footprints and most are intrachromosomal. Multiple rearrangement architectures are present, but tandem duplications are particularly common in some cancers, perhaps reflecting a specific defect in DNA maintenance. Short overlapping sequences at most rearrangement junctions indicate that these have been mediated by non-homologous end-joining DNA repair, although varying sequence patterns indicate that multiple processes of this type are operative. Several expressed in-frame fusion genes were identified but none was recurrent. The study provides a new perspective on cancer genomes, highlighting the diversity of somatic rearrangements and their potential contribution to cancer development.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.forename: David J
authors.initials: DJ
authors.lastname: McBride
authors.forename: Meng-Lay
authors.initials: ML
authors.lastname: Lin
authors.forename: Ignacio
authors.initials: I
authors.lastname: Varela
authors.forename: Erin D
authors.initials: ED
authors.lastname: Pleasance
authors.forename: Jared T
authors.initials: JT
authors.lastname: Simpson
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Stebbings
authors.forename: Catherine
authors.initials: C
authors.lastname: Leroy
authors.forename: Sarah
authors.initials: S
authors.lastname: Edkins
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Mudie
authors.forename: Chris D
authors.initials: CD
authors.lastname: Greenman
authors.forename: Mingming
authors.initials: M
authors.lastname: Jia
authors.forename: Calli
authors.initials: C
authors.lastname: Latimer
authors.forename: Jon W
authors.initials: JW
authors.lastname: Teague
authors.forename: King Wai
authors.initials: KW
authors.lastname: Lau
authors.forename: John
authors.initials: J
authors.lastname: Burton
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quail
authors.forename: Harold
authors.initials: H
authors.lastname: Swerdlow
authors.forename: Carol
authors.initials: C
authors.lastname: Churcher
authors.forename: Rachael
authors.initials: R
authors.lastname: Natrajan
authors.forename: Anieta M
authors.initials: AM
authors.lastname: Sieuwerts
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Silver
authors.forename: Anita
authors.initials: A
authors.lastname: Langerød
authors.forename: Hege E G
authors.initials: HE
authors.lastname: Russnes
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.forename: Laura
authors.initials: L
authors.lastname: van 't Veer
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Richardson
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Campbell
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Futreal
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D053960:DNA Breaks; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D015698:Genomic Library; D006801:Humans; D017422:Sequence Analysis, DNA