Mass homozygotes accumulation in the NCI-60 cancer cell lines as compared to HapMap Trios, and relation to fragile site location - PubMed (original) (raw)

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

Xiaoyang Ruan et al. PLoS One. 2012.

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. NCI-60 and HapMap ROH pattern, and miRNA, FRA position.

Red arrows on the right indicate the FRAs with average upper 95th percentile ROHF larger than 0.5 in a ±5 Mb vicinity. Red asterisks indicate high ROHF bands (average upper 95th percentile ROHF>0.6) without FRA in ±5 Mb vicinity. Rare FRAs are marked by red color. The gaps between the sections of the chromosomes (for example at 130 Mb nucleotides in chromosome 1) contain the centromere. The top portion corresponds to p arm, and bottom portion corresponds to q arm.

Figure 2

Figure 2. Genes involved in chemotaxis.

Pathway analysis on SNPs with top ROHF difference between adult and young subgroups show the involvement of chemotaxis process. Red solid circles show genes covering SNPs with top change (see statistics section for details).

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References

    1. Knudson AG. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971;68:820–823. - PMC - PubMed
    1. Knudson AG. Two genetic hits (more or less) to cancer. Nat Rev Cancer. 2001;1:157–162. - PubMed
    1. Shen P, Huang HV. Homologous recombination in Escherichia coli: dependence on substrate length and homology. Genetics. 1986;112:441–457. - PMC - PubMed
    1. Barnes RL, McCulloch R. Trypanosoma brucei homologous recombination is dependent on substrate length and homology, though displays a differential dependence on mismatch repair as substrate length decreases. Nucleic Acids Res. 2007;35:3478–3493. - PMC - PubMed
    1. Shao C, Stambrook PJ, Tischfield JA. Mitotic recombination is suppressed by chromosomal divergence in hybrids of distantly related mouse strains. Nat Genet. 2001;28:169–172. - PubMed

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