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Genome-wide genetic and epigenetic analyses of pancreatic acinar cell carcinomas reveal aberrations in genome stability

Author

Listed:
  • Cornelia Jäkel

    (German Cancer Research Center (DKFZ))

  • Frank Bergmann

    (University Hospital Heidelberg)

  • Reka Toth

    (German Cancer Research Center (DKFZ))

  • Yassen Assenov

    (German Cancer Research Center (DKFZ))

  • Daniel Duin

    (German Cancer Research Center (DKFZ))

  • Oliver Strobel

    (University Hospital Heidelberg)

  • Thomas Hank

    (University Hospital Heidelberg)

  • Günter Klöppel

    (Technical University Munich)

  • Craig Dorrell

    (Oregon Health and Science University)

  • Markus Grompe

    (Oregon Health and Science University)

  • Joshua Moss

    (The Hebrew University-Hadassah Medical School)

  • Yuval Dor

    (The Hebrew University-Hadassah Medical School)

  • Peter Schirmacher

    (University Hospital Heidelberg)

  • Christoph Plass

    (German Cancer Research Center (DKFZ))

  • Odilia Popanda

    (German Cancer Research Center (DKFZ))

  • Peter Schmezer

    (German Cancer Research Center (DKFZ))

Abstract

Pancreatic acinar cell carcinoma (ACC) is an aggressive exocrine tumor with largely unknown biology. Here, to identify potential targets for personalized treatment, we perform integrative genome-wide and epigenome-wide analyses. The results show frequently aberrant DNA methylation, abundant chromosomal amplifications and deletions, and mutational signatures suggesting defective DNA repair. In contrast to pancreatic ductal adenocarcinoma, no recurrent point mutations are detected. The tumor suppressors ID3, ARID1A, APC, and CDKN2A are frequently impaired also on the protein level and thus potentially affect ACC tumorigenesis. Consequently, this work identifies promising therapeutic targets in ACC for drugs recently approved for precision cancer therapy.

Suggested Citation

  • Cornelia Jäkel & Frank Bergmann & Reka Toth & Yassen Assenov & Daniel Duin & Oliver Strobel & Thomas Hank & Günter Klöppel & Craig Dorrell & Markus Grompe & Joshua Moss & Yuval Dor & Peter Schirmacher, 2017. "Genome-wide genetic and epigenetic analyses of pancreatic acinar cell carcinomas reveal aberrations in genome stability," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01118-x
    DOI: 10.1038/s41467-017-01118-x
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