Skip to main content

Genome-Wide Analysis of Palindrome Formation with Next-Generation Sequencing (GAPF-Seq) and a Bioinformatics Pipeline for Assessing De Novo Palindromes in Cancer Genomes

  • Protocol
  • First Online:
Cancer Systems and Integrative Biology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2660))

Abstract

DNA palindromes are a type of chromosomal aberration that appears frequently during tumorigenesis. They are characterized by sequences of nucleotides that are identical to their reverse complements and often arise due to illegitimate repair of DNA double-strand breaks, fusion of telomeres, or stalled replication forks, all of which are common adverse early events in cancer. Here, we describe the protocol for enriching palindromes from genomic DNA sources with low-input DNA amounts and detail a bioinformatics tool for assessing the enrichment and location of de novo palindrome formation from low-coverage whole-genome sequencing data.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Li Y, Roberts ND, Wala JA, Shapira O, Schumacher SE, Kumar K, Khurana E, Waszak S, Korbel JO, Haber JE, Imielinski M, Akdemir KC, Alvarez EG, Baez-Ortega A, Beroukhim R, Boutros PC, Bowtell DDI, Brors B, Burns KH, Campbell PJ, Chan K, Chen K, Cortés-Ciriano I, Dueso-Barroso A, Dunford AJ, Edwards PA, Estivill X, Etemadmoghadam D, Feuerbach L, Fink JL, Frenkel-Morgenstern M, Garsed DW, Gerstein M, Gordenin DA, Haan D, Haber JE, Hess JM, Hutter B, Imielinski M, Jones DTW, Ju YS, Kazanov MD, Klimczak LJ, Koh Y, Korbel JO, Kumar K, Lee EA, Lee JJK, Li Y, Lynch AG, Macintyre G, Markowetz F, Martincorena I, Martinez-Fundichely A, Meyerson M, Miyano S, Nakagawa H, Navarro FCP, Ossowski S, Park PJ, Pearson JV, Puiggròs M, Rippe K, Roberts ND, Roberts SA, Rodriguez-Martin B, Schumacher SE, Scully R, Shackleton M, Sidiropoulos N, Sieverling L, Stewart C, Torrents D, Tubio JMC, Villasante I, Waddell N, Wala JA, Weischenfeldt J, Yang L, Yao X, Yoon SS, Zamora J, Zhang CZ, Weischenfeldt J, Beroukhim R, Campbell PJ, P.S.V.W. Group, and P. Consortium (2020) Patterns of somatic structural variation in human cancer genomes. Nature 578(7793):112–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hellman A, Zlotorynski E, Scherer SW, Cheung J, Vincent JB, Smith DI, Trakhtenbrot L, Kerem B (2002) A role for common fragile site induction in amplification of human oncogenes. Cancer Cell 1(1):89–97

    Article  CAS  PubMed  Google Scholar 

  3. Tanaka H, Watanabe T (2020) Mechanisms underlying recurrent genomic amplification in human cancers. Trends Cancer 6(6):462–477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Marotta M, Chen X, Watanabe T, Faber PW, Diede SJ, Tapscott S, Tubbs R, Kondratova A, Stephens R, Tanaka H (2013) Homology-mediated end-capping as a primary step of sister chromatid fusion in the breakage-fusion-bridge cycles. Nucleic Acids Res 41(21):9732–9740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rudolph KL, Millard M, Bosenberg MW, DePinho RA (2001) Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nat Genet 28(2):155–159

    Article  CAS  PubMed  Google Scholar 

  6. Coquelle A, Pipiras E, Toledo F, Buttin G, Debatisse M (1997) Expression of fragile sites triggers intrachromosomal mammalian gene amplification and sets boundaries to early amplicons. Cell 89(2):215–225

    Article  CAS  PubMed  Google Scholar 

  7. Tanaka H, Tapscott SJ, Trask BJ, Yao MC (2002) Short inverted repeats initiate gene amplification through the formation of a large DNA palindrome in mammalian cells. Proc Natl Acad Sci U S A 99(13):8772–8777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Maser RS, DePinho RA (2002) Connecting chromosomes, crisis, and cancer. Science 297(5581):565–569

    Article  CAS  PubMed  Google Scholar 

  9. Marotta M, Onodera T, Johnson J, Budd GT, Watanabe T, Cui X, Giuliano AE, Niida A, Tanaka H (2017) Palindromic amplification of the ERBB2 oncogene in primary HER2-positive breast tumors. Sci Rep 7:41921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tanaka H, Bergstrom DA, Yao MC, Tapscott SJ (2005) Widespread and nonrandom distribution of DNA palindromes in cancer cells provides a structural platform for subsequent gene amplification. Nat Genet 37(3):320–327

    Article  CAS  PubMed  Google Scholar 

  11. Guenthoer J, Diede SJ, Tanaka H, Chai X, Hsu L, Tapscott SJ, Porter PL (2012) Assessment of palindromes as platforms for DNA amplification in breast cancer. Genome Res 22(2):232–245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Diede SJ, Guenthoer J, Geng LN, Mahoney SE, Marotta M, Olson JM, Tanaka H, Sj T (2010) DNA methylation of developmental genes in pediatric medulloblastomas identified by denaturation analysis of methylation differences. Proc Natl Acad Sci U S A 107(1):234–239

    Article  CAS  PubMed  Google Scholar 

  13. Yang H, Volfovsky N, Rattray A, Chen X, Tanaka H, Strathern J (2014) GAP-Seq: a method for identification of DNA palindromes. BMC Genomics 15:394

    Article  PubMed  PubMed Central  Google Scholar 

  14. Rattray AJ (2004) A method for cloning and sequencing long palindromic DNA junctions. Nucleic Acids Res 32(19):e155

    Article  PubMed  PubMed Central  Google Scholar 

  15. Papageorgiou L, Eleni P, Raftopoulou S, Mantaiou M, Megalooikonomou V, Vlachakis D (2018) Genomic big data hitting the storage bottleneck. EMBnet J 24:e910

    Article  PubMed  PubMed Central  Google Scholar 

  16. Warburton PE, Giordano J, Cheung F, Gelfand Y, Benson G (2004) Inverted repeat structure of the human genome: the X-chromosome contains a preponderance of large, highly homologous inverted repeats that contain testes genes. Genome Res 14(10A):1861–1869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work is supported by the National Cancer Institute (2 R01 CA149385), Department of Defense (W81XWH-18-1-0058), Cedars-Sinai Medical Center (to H.T.), and the Margie and Robert E. Petersen Foundation (to A.E.G.).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Michael M. Murata or Hisashi Tanaka .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Murata, M.M., Giuliano, A.E., Tanaka, H. (2023). Genome-Wide Analysis of Palindrome Formation with Next-Generation Sequencing (GAPF-Seq) and a Bioinformatics Pipeline for Assessing De Novo Palindromes in Cancer Genomes. In: Kasid, U.N., Clarke, R. (eds) Cancer Systems and Integrative Biology. Methods in Molecular Biology, vol 2660. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3163-8_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-3163-8_2

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3162-1

  • Online ISBN: 978-1-0716-3163-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics