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Mass homozygotes accumulation in the NCI-60 cancer cell lines as compared to HapMap Trios, and relation to fragile site location.

Xiaoyang Ruan | Jean-Pierre A Kocher | Yves Pommier | Hongfang Liu | William C Reinhold
PloS one | 2012

Runs of homozygosity (ROH) represents extended length of homozygotes on a long genomic distance. In oncology, it is known as loss of heterozygosity (LOH) if identified exclusively in cancer cell rather than in matched control cell. Studies have identified several genomic regions which show consistent ROH in different kinds of carcinoma. To query whether this consistency can be observed on broader spectrum, both in more cancer types and in wider genomic regions, we investigated ROH patterns in the National Cancer Institute 60 cancer cell line panel (NCI-60) and HapMap Caucasian healthy trio families. Using results from Affymetrix 500 K SNP arrays, we report a genome wide significant association of ROH regions between the NCI-60 and HapMap samples, with much a higher level of ROH (11 fold) in the cancer cell lines. Analysis shows that more severe ROH found in cancer cells appears to be the extension of existing ROH in healthy state. In the HapMap trios, the adult subgroup had a slightly but significantly higher level (1.02 fold) of ROH than did the young subgroup. For several ROH regions we observed the co-occurrence of fragile sites (FRAs). However, FRA on the genome wide level does not show a clear relationship with ROH regions.

Pubmed ID: 22347499

Research resources used in this publication

None found

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Associated grants

  • Agency: NLM NIH HHS, United States
    Id: R01 LM009959
  • Agency: NLM NIH HHS, United States
    Id: R01LM009959A1
  • Agency: Intramural NIH HHS, United States

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PLINK (tool)

RRID:SCR_001757

Open source whole genome association analysis toolset, designed to perform range of basic, large scale analyses in computationally efficient manner. Used for analysis of genotype/phenotype data. Through integration with gPLINK and Haploview, there is some support for subsequent visualization, annotation and storage of results. PLINK 1.9 is improved and second generation of the software.

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NCI National Products Branch (tool)

RRID:SCR_010603

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miRBase (tool)

RRID:SCR_003152

Central online repository for microRNA nomenclature, sequence data, annotation and target prediction.Collection of published miRNA sequences and annotation.

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RRID:SCR_002473

Database for genomes that have been completely sequenced, have active research community to contribute gene-specific information, or that are scheduled for intense sequence analysis. Includes nomenclature, map location, gene products and their attributes, markers, phenotypes, and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases. All entries follow NCBI's format for data collections. Content of Entrez Gene represents result of curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases, and from many other databases available from NCBI. Records are assigned unique, stable and tracked integers as identifiers. Content is updated as new information becomes available.

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CellMiner (tool)

RRID:SCR_025648

Database and query tool designed for cancer research community to facilitate integration and study of molecular and pharmacological data for the NCI-60 cancerous cell lines. The NCI-60, panel of 60 diverse human cancer cell lines used by the Developmental Therapeutics Program of the U.S. National Cancer Institute to screen over 100,000 chemical compounds and natural products since 1990.

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RRID:CVCL_0465

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