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Widespread and nonrandom distribution of DNA palindromes in cancer cells provides a structural platform for subsequent gene amplification

Nature Genetics volume 37, pages 320–327 (2005)Cite this article

A Corrigendum to this article was published on 01 April 2010

Abstract

Breakage-fusion-bridge cycles contribute to chromosome instability and generate large DNA palindromes that facilitate gene amplification in human cancers. The prevalence of large DNA palindromes in cancer is not known. Here, by using a new microarray-based approach called genome-wide analysis of palindrome formation, we show that palindromes occur frequently and are widespread in human cancers. Individual tumors seem to have a nonrandom distribution of palindromes in their genomes, and a subset of palindromic loci is associated with gene amplification. This indicates that the location of palindromes in the cancer genome can serve as a structural platform that supports subsequent gene amplification. Genome-wide analysis of palindrome formation is a new approach to identify structural chromosome aberrations associated with cancer.

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Figure 1: Snap-back DNA and S1 digestion enriches for palindromic DNA.
Figure 2: GAPF.
Figure 3: GAPF-positive features are not randomly distributed in cancer cells.
Figure 4: Physical maps of GAPF-positive cytogenetic bands.
Figure 5: Palindromic amplification of ECM1 in Colo320DM cells.

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Acknowledgements

We thank J. Delrow and the Fred Hutchinson Cancer Research Center Genomics facility for advice on the array studies and P. Nieman, M. Groudine, B. Trask, C. Kemp, J. Radich, J. Roberts and members of the laboratory of M.-C.Y. for comments on the manuscripts. This work was supported by National Institutes of Health grants from General Medicine (M.-C.Y.) and National Institute of Arthritis, Musculoskeletal and Skin Diseases (S.J.T.) and by the Avon Breast Cancer Crusade Opportunity Fund (to H.T.). H.T. is a recipient of Interdisciplinary Dual Mentor Fellowship of Fred Hutchinson Cancer Research Center (1999 and 2001).

Author information

Authors and Affiliations

  1. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Hisashi Tanaka & Meng-Chao Yao

  2. Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA

    Donald A Bergstrom

  3. Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan

    Meng-Chao Yao

  4. Division of Human Biology, Fred Hutchinson Cancer Research Center, Mailstop C3-168, 1100 Fairview Avenue North, Seattle, 98109-1024, Washington, USA

    Stephen J Tapscott

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  1. Hisashi Tanaka
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Correspondence to Meng-Chao Yao or Stephen J Tapscott.

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Supplementary information

Supplementary Fig. 1

MYC is amplified in a large DNA palindrome in Colo320DM. (PDF 193 kb)

Supplementary Fig. 2

Restriction map for the ECM1 gene. (PDF 186 kb)

Supplementary Fig. 3

Cot-1 DNA suppresses hybridization of repetitive sequences. (PDF 155 kb)

Supplementary Table 1

GAPF-positive cytogenetic bands (q-value <0.05 and positive fold-change) in Colo320DM, MCF7, RD and medulloblastomas, and GAPF-positive 5MB bins in Colo320DM and MCF7. (PDF 133 kb)

Supplementary Table 2

GAPF features of genes in three GAPF-positive cytogenetic bands (8q24.1, 1q21 and 7q35) in Colo and MCF7. (PDF 298 kb)

Supplementary Table 3

GAPF-positive genes. (PDF 78 kb)

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Tanaka, H., Bergstrom, D., Yao, MC. et al. Widespread and nonrandom distribution of DNA palindromes in cancer cells provides a structural platform for subsequent gene amplification. Nat Genet 37, 320–327 (2005). https://doi.org/10.1038/ng1515

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