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
N1 - Publisher Copyright:
© 2017 The Author(s).
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
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C2 - 29109526
AN - SCOPUS:85032934700
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1323
ER -
