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

Cornelia Jäkel; Frank Bergmann; Reka Toth; Yassen Assenov; Daniel Van Der Duin; Oliver Strobel; Thomas Hank; Günter Klöppel; Craig Dorrell; Markus Grompe; Joshua Moss; Yuval Dor; Peter Schirmacher; Christoph Plass; Odilia Popanda; Peter Schmezer

doi:10.1038/s41467-017-01118-x

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

Cornelia Jäkel, Frank Bergmann, Reka Toth, Yassen Assenov, Daniel Van Der Duin, Oliver Strobel, Thomas Hank, Günter Klöppel, Craig Dorrell, Markus Grompe, Joshua Moss, Yuval Dor, Peter Schirmacher, Christoph Plass, Odilia Popanda, Peter Schmezer^*

^*Corresponding author for this work

Department of Developmental Biology and Cancer Research

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

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.

Original language	English
Article number	1323
Journal	Nature Communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-01118-x
State	Published - 1 Dec 2017

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© 2017 The Author(s).

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Jäkel, C., Bergmann, F., Toth, R., Assenov, Y., Van Der Duin, D., Strobel, O., Hank, T., Klöppel, G., Dorrell, C., Grompe, M., Moss, J., Dor, Y., Schirmacher, P., Plass, C., Popanda, O., & Schmezer, P. (2017). Genome-wide genetic and epigenetic analyses of pancreatic acinar cell carcinomas reveal aberrations in genome stability. Nature Communications, 8(1), Article 1323. https://doi.org/10.1038/s41467-017-01118-x

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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.",

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Jäkel, C, Bergmann, F, Toth, R, Assenov, Y, Van Der Duin, D, Strobel, O, Hank, T, Klöppel, G, Dorrell, C, Grompe, M, Moss, J, Dor, Y, Schirmacher, P, Plass, C, Popanda, O & Schmezer, P 2017, 'Genome-wide genetic and epigenetic analyses of pancreatic acinar cell carcinomas reveal aberrations in genome stability', Nature Communications, vol. 8, no. 1, 1323. https://doi.org/10.1038/s41467-017-01118-x

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AU - Jäkel, Cornelia

AU - Bergmann, Frank

AU - Toth, Reka

AU - Assenov, Yassen

AU - Van Der Duin, Daniel

AU - Strobel, Oliver

AU - Hank, Thomas

AU - Klöppel, Günter

AU - Dorrell, Craig

AU - Grompe, Markus

AU - Moss, Joshua

AU - Dor, Yuval

AU - Schirmacher, Peter

AU - Plass, Christoph

AU - Popanda, Odilia

AU - Schmezer, Peter

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N2 - 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.

AB - 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.

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

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