Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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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Publications

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]

PMID: 21467267

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Project description:Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIA-PET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated noncoding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells. RNA polymerase II (RNAPII) bound chromatin interactions were extracted with Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) sequencing, in order to study the transcription regulations with RNAPII-associated long-range chromatin interactions. Five cell lines, namely MCF7 (ATCC# HTB-22), K562 (ATCC# CCL-243), HCT116 (ATCC# CCL-247), HeLa (ATCC# CCL-2.2), and NB4 (Roussel and Lanotte, 2001) (provided by Dr. Sherman Weissman, Yale University), were grown under standard culture conditions and harvested at log phase. Harvested cells were cross-linked using 1% formaldehyde followed by neutralization with 0.2M glycine. Chromatin was isolated and subjected to ChIA-PET protocol as described in Fullwood et al (Fullwood et al: An oestrogen-receptor-alpha-bound human chromatin interactome. Nature 2009, 462(7269):58-64). The ChIA-PET sequence reads were processed and analyzed using ChIA-PET Tool (Li et al: ChIA-PET tool for comprehensive chromatin interaction analysis with paired-end tag sequencing. Genome Biol 2010, 11(2):R22).

Dataset Information

Comprehensive Long Span Paired-End-Tag Mapping Reveals Characteristic Patterns of Structural Variations in Epithelial Cancer Genomes

Publications

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

Similar Datasets

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