title: Comprehensive long-span paired-end-tag mapping reveals characteristic patterns of structural variations in epithelial cancer genomes.
abstract: Somatic genome rearrangements are thought to play important roles in cancer development. We optimized a long-span paired-end-tag (PET) sequencing approach using 10-Kb genomic DNA inserts to study human genome structural variations (SVs). The use of a 10-Kb insert size allows the identification of breakpoints within repetitive or homology-containing regions of a few kilobases in size and results in a higher physical coverage compared with small insert libraries with the same sequencing effort. We have applied this approach to comprehensively characterize the SVs of 15 cancer and two noncancer genomes and used a filtering approach to strongly enrich for somatic SVs in the cancer genomes. Our analyses revealed that most inversions, deletions, and insertions are germ-line SVs, whereas tandem duplications, unpaired inversions, interchromosomal translocations, and complex rearrangements are over-represented among somatic rearrangements in cancer genomes. We demonstrate that the quantitative and connective nature of DNA-PET data is precise in delineating the genealogy of complex rearrangement events, we observe signatures that are compatible with breakage-fusion-bridge cycles, and we discover that large duplications are among the initial rearrangements that trigger genome instability for extensive amplification in epithelial cancers.
authors.affiliation: Genome Technology and Biology, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Axel M
authors.initials: AM
authors.lastname: Hillmer
authors.forename: Fei
authors.initials: F
authors.lastname: Yao
authors.forename: Koichiro
authors.initials: K
authors.lastname: Inaki
authors.forename: Wah Heng
authors.initials: WH
authors.lastname: Lee
authors.forename: Pramila N
authors.initials: PN
authors.lastname: Ariyaratne
authors.forename: Audrey S M
authors.initials: AS
authors.lastname: Teo
authors.forename: Xing Yi
authors.initials: XY
authors.lastname: Woo
authors.forename: Zhenshui
authors.initials: Z
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhao
authors.forename: Leena
authors.initials: L
authors.lastname: Ukil
authors.forename: Jieqi P
authors.initials: JP
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Jimmy B Y
authors.initials: JB
authors.lastname: So
authors.forename: Manuel
authors.initials: M
authors.lastname: Salto-Tellez
authors.forename: Wan Ting
authors.initials: WT
authors.lastname: Poh
authors.forename: Kelson F B
authors.initials: KF
authors.lastname: Zawack
authors.forename: Niranjan
authors.initials: N
authors.lastname: Nagarajan
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.forename: Guoliang
authors.initials: G
authors.lastname: Li
authors.forename: Vikrant
authors.initials: V
authors.lastname: Kumar
authors.forename: Hui Ping J
authors.initials: HP
authors.lastname: Lim
authors.forename: Yee Yen
authors.initials: YY
authors.lastname: Sia
authors.forename: Chee Seng
authors.initials: CS
authors.lastname: Chan
authors.forename: See Ting
authors.initials: ST
authors.lastname: Leong
authors.forename: Say Chuan
authors.initials: SC
authors.lastname: Neo
authors.forename: Poh Sum D
authors.initials: PS
authors.lastname: Choi
authors.forename: Hervé
authors.initials: H
authors.lastname: Thoreau
authors.forename: Patrick B O
authors.initials: PB
authors.lastname: Tan
authors.forename: Atif
authors.initials: A
authors.lastname: Shahab
authors.forename: Xiaoan
authors.initials: X
authors.lastname: Ruan
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Per
authors.initials: P
authors.lastname: Hall
authors.forename: Valère
authors.initials: V
authors.lastname: Cacheux-Rataboul
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Wei
authors.forename: Khay Guan
authors.initials: KG
authors.lastname: Yeoh
authors.forename: Wing-Kin
authors.initials: WK
authors.lastname: Sung
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bourque
authors.forename: Edison T
authors.initials: ET
authors.lastname: Liu
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
mesh_terms: D020029:Base Pairing / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D002874:Chromosome Mapping / Q000379:methods*; D019295:Computational Biology; D004247:DNA / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D015894:Genome, Human / Q000235:genetics*; D056914:Genomic Structural Variation / Q000235:genetics*; D006801:Humans; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D004247:DNA