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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 10 Kb insert size allows the identification of breakpoints within repetitive or homology containing regions of a few Kb in size and results in a higher physical coverage compared to small insert libraries with the same sequencing effort. We have applied this approach to comprehensively characterize the SVs of 15 cancer and 2 non-cancer 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 germline SVs, whereas tandem duplications, unpaired inversions, inter-chromosomal translocations, and complex rearrangements are overrepresented 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 which are compatible with breakage-fusion-bridge cycles, and discover that large duplications are among the initial rearrangements that trigger genome instability for extensive amplification in epithelial cancers. Structural variations of 15 human cancer samples and 2 human normal samples were identified by long span paired-end sequencing

ORGANISM(S): Homo sapiens

SUBMITTER: Axel HILLMER 

PROVIDER: E-GEOD-26954 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Hillmer Axel M AM   Yao Fei F   Inaki Koichiro K   Lee Wah Heng WH   Ariyaratne Pramila N PN   Teo Audrey S M AS   Woo Xing Yi XY   Zhang Zhenshui Z   Zhao Hao H   Ukil Leena L   Chen Jieqi P JP   Zhu Feng F   So Jimmy B Y JB   Salto-Tellez Manuel M   Poh Wan Ting WT   Zawack Kelson F B KF   Nagarajan Niranjan N   Gao Song S   Li Guoliang G   Kumar Vikrant V   Lim Hui Ping J HP   Sia Yee Yen YY   Chan Chee Seng CS   Leong See Ting ST   Neo Say Chuan SC   Choi Poh Sum D PS   Thoreau Hervé H   Tan Patrick B O PB   Shahab Atif A   Ruan Xiaoan X   Bergh Jonas J   Hall Per P   Cacheux-Rataboul Valère V   Wei Chia-Lin CL   Yeoh Khay Guan KG   Sung Wing-Kin WK   Bourque Guillaume G   Liu Edison T ET   Ruan Yijun Y  

Genome research 20110405 5


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  ...[more]

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