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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

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  • Xiaoyang Ruan
  • Jean-Pierre A Kocher
  • Yves Pommier
  • Hongfang Liu
  • William C Reinhold

Abstract

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.

Suggested Citation

  • Xiaoyang Ruan & Jean-Pierre A Kocher & Yves Pommier & Hongfang Liu & William C Reinhold, 2012. "Mass Homozygotes Accumulation in the NCI-60 Cancer Cell Lines As Compared to HapMap Trios, and Relation to Fragile Site Location," PLOS ONE, Public Library of Science, vol. 7(2), pages 1-9, February.
    • Handle: RePEc:plo:pone00:0031628
    DOI: 10.1371/journal.pone.0031628
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    1. Rameen Beroukhim & Ming Lin & Yuhyun Park & Ke Hao & Xiaojun Zhao & Levi A Garraway & Edward A Fox & Ephraim P Hochberg & Ingo K Mellinghoff & Matthias D Hofer & Aurelien Descazeaud & Mark A Rubin & M, 2006. "Inferring Loss-of-Heterozygosity from Unpaired Tumors Using High-Density Oligonucleotide SNP Arrays," PLOS Computational Biology, Public Library of Science, vol. 2(5), pages 1-10, May.
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