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.
Bibliographical noteFunding Information:
We thank the microarray unit and the high-throughput sequencing unit of the DKFZ Genomics and Proteomics Core Facility for providing the Illumina HumanMethylation 450 arrays, performing whole-exome sequencing and related services. We thank the Data Management and Genomics IT from the eilslabs for aligning sequencing data and calling SNVs. Funding for this study comes in part from the German Cancer Consortium (DKTK) and the Helmholtz Foundation.
© 2017 The Author(s).