title: A sequence-based survey of the complex structural organization of tumor genomes.
abstract: BACKGROUND
  The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using end sequencing profiling, which relies on paired-end sequencing of cloned tumor genomes.
  
  
  RESULTS
  In the present study brain, breast, ovary, and prostate tumors, along with three breast cancer cell lines, were surveyed using end sequencing profiling, yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent. Sequencing and fluorescence in situ hybridization confirmed translocations and complex tumor genome structures that include co-amplification and packaging of disparate genomic loci with associated molecular heterogeneity. Comparison of the tumor genomes suggests recurrent rearrangements. Some are likely to be novel structural polymorphisms, whereas others may be bona fide somatic rearrangements. A recurrent fusion transcript in breast tumors and a constitutional fusion transcript resulting from a segmental duplication were identified. Analysis of end sequences for single nucleotide polymorphisms revealed candidate somatic mutations and an elevated rate of novel single nucleotide polymorphisms in an ovarian tumor.
  
  
  CONCLUSIONS
  These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than was previously appreciated and that genomic fusions, including fusion transcripts and proteins, may be common, possibly yielding tumor-specific biomarkers and therapeutic targets.
authors: Department of Computer Science & Center for Computational Molecular Biology, Brown University, Waterman Street, Providence, RI 02912-1910, USA. braphael@brown.edu
authors: Benjamin J
authors: BJ
authors: Raphael
authors: Stanislav
authors: S
authors: Volik
authors: Peng
authors: P
authors: Yu
authors: Chunxiao
authors: C
authors: Wu
authors: Guiqing
authors: G
authors: Huang
authors: Elena V
authors: EV
authors: Linardopoulou
authors: Barbara J
authors: BJ
authors: Trask
authors: Frederic
authors: F
authors: Waldman
authors: Joseph
authors: J
authors: Costello
authors: Kenneth J
authors: KJ
authors: Pienta
authors: Gordon B
authors: GB
authors: Mills
authors: Krystyna
authors: K
authors: Bajsarowicz
authors: Yasuko
authors: Y
authors: Kobayashi
authors: Shivaranjani
authors: S
authors: Sridharan
authors: Pamela L
authors: PL
authors: Paris
authors: Quanzhou
authors: Q
authors: Tao
authors: Sarah J
authors: SJ
authors: Aerni
authors: Raymond P
authors: RP
authors: Brown
authors: Ali
authors: A
authors: Bashir
authors: Joe W
authors: JW
authors: Gray
authors: Jan-Fang
authors: JF
authors: Cheng
authors: Pieter
authors: P
authors: de Jong
authors: Mikhail
authors: M
authors: Nefedov
authors: Thomas
authors: T
authors: Ried
authors: Hesed M
authors: HM
authors: Padilla-Nash
authors: Colin C
authors: CC
authors: Collins
mesh_terms: D002277:Carcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial; D053960:DNA Breaks; D015723:Gene Library; D023061:Gene Order; D052138:Genes, Neoplasm; D015894:Genome, Human; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic