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

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

54 Citations (Scopus)

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
Publication status	Published - 1 Dec 2017
Externally published	Yes

Access to Document

10.1038/s41467-017-01118-x

Cite this

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

@article{03a88eca863948b398b0e1507aa16089,

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

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.",

author = "Cornelia J{\"a}kel and Frank Bergmann and Reka Toth and Yassen Assenov and {Van Der Duin}, Daniel and Oliver Strobel and Thomas Hank and G{\"u}nter Kl{\"o}ppel and Craig Dorrell and Markus Grompe and Joshua Moss and Yuval Dor and Peter Schirmacher and Christoph Plass and Odilia Popanda and Peter Schmezer",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/s41467-017-01118-x",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

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

TY - JOUR

T1 - Genome-wide genetic and epigenetic analyses of pancreatic acinar cell carcinomas reveal aberrations in genome stability

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

PY - 2017/12/1

Y1 - 2017/12/1

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.

UR - http://www.scopus.com/inward/record.url?scp=85032934700&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-01118-x

DO - 10.1038/s41467-017-01118-x

M3 - Article

C2 - 29109526

AN - SCOPUS:85032934700

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1323

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this