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

Research output: Contribution to journalArticle

13 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 languageEnglish (US)
Article number1323
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Acinar Cell Carcinoma
genome
Genomic Instability
Aberrations
Epigenomics
Tumors
aberration
Genes
cancer
Cells
Genome
Amplification
Neoplasms
Repair
tumors
deoxyribonucleic acid
DNA Methylation
Point Mutation
suppressors
DNA Repair

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Jäkel, C., Bergmann, F., Toth, R., Assenov, Y., Van Der Duin, D., Strobel, O., ... Schmezer, P. (2017). Genome-wide genetic and epigenetic analyses of pancreatic acinar cell carcinomas reveal aberrations in genome stability. Nature Communications, 8(1), [1323]. https://doi.org/10.1038/s41467-017-01118-x

Genome-wide genetic and epigenetic analyses of pancreatic acinar cell carcinomas reveal aberrations in genome stability. / Jäkel, Cornelia; Bergmann, Frank; Toth, Reka; Assenov, Yassen; Van Der Duin, Daniel; Strobel, Oliver; Hank, Thomas; Klöppel, Günter; Dorrell, Craig; Grompe, Markus; Moss, Joshua; Dor, Yuval; Schirmacher, Peter; Plass, Christoph; Popanda, Odilia; Schmezer, Peter.

In: Nature Communications, Vol. 8, No. 1, 1323, 01.12.2017.

Research output: Contribution to journalArticle

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
Jäkel, Cornelia ; Bergmann, Frank ; Toth, Reka ; Assenov, Yassen ; Van Der Duin, Daniel ; Strobel, Oliver ; Hank, Thomas ; Klöppel, Günter ; Dorrell, Craig ; Grompe, Markus ; Moss, Joshua ; Dor, Yuval ; Schirmacher, Peter ; Plass, Christoph ; Popanda, Odilia ; Schmezer, Peter. / Genome-wide genetic and epigenetic analyses of pancreatic acinar cell carcinomas reveal aberrations in genome stability. In: Nature Communications. 2017 ; Vol. 8, No. 1.
@article{c22d11400e7c4091a96da396b75bb3f2,
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",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41467-017-01118-x",
language = "English (US)",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

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

UR - http://www.scopus.com/inward/citedby.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

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1323

ER -