Comprehensive long-span paired-end-tag mapping reveals characteristic patterns of structural variations in epithelial cancer genomes

Axel M. Hillmer, Fei Yao, Koichiro Inaki, Wah Heng Lee, Pramila N. Ariyaratne, Audrey S M Teo, Xing Yi Woo, Zhenshui Zhang, Hao Zhao, Leena Ukil, Jieqi P. Chen, Feng Zhu, Jimmy B Y So, Manuel Salto-Tellez, Wan Ting Poh, Kelson F B Zawack, Niranjan Nagarajan, Song Gao, Guoliang Li, Vikrant KumarHui Ping J Lim, Yee Yen Sia, Chee Seng Chan, See Ting Leong, Say Chuan Neo, Poh Sum D Choi, Hervé Thoreau, Patrick B O Tan, Atif Shahab, Xiaoan Ruan, Jonas Bergh, Per Hall, Valère Cacheux-Rataboul, Chia Lin Wei, Khay Guan Yeoh, Wing Kin Sung, Guillaume Bourque, Edison T. Liu, Yijun Ruan

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)665-675
Number of pages11
JournalGenome Research
Issue number5
Publication statusPublished or Issued - May 2011

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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