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Nat Commun. 2017 Nov 6;8(1):1323. doi: 10.1038/s41467-017-01118-x.

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

Author information

1
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
2
Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
3
Department of General and Visceral Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
4
Institute of Pathology, Technical University Munich, Trogerstr. 18, 81675, Munich, Germany.
5
Department of Pediatrics, Papé Family Pediatric Research Institute, Oregon Stem Cell Center, Oregon Health and Science University, Portland, OR, 97239, USA.
6
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, 9112102, Jerusalem, Israel.
7
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. p.schmezer@dkfz.de.

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.

PMID:
29109526
PMCID:
PMC5673892
DOI:
10.1038/s41467-017-01118-x
[Indexed for MEDLINE]
Free PMC Article

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