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

• DOI: 10.1038/s41467-017-01118-x
• Publication Date: 2017-10-31T15:13:26Z
• Authors: 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
• Keywords: Chromosome Aberrations; 0303 health sciences; Carcinoma, Acinar Cell; Science; Q; Gene Dosage; Cell Cycle Checkpoints; Article; Genomic Instability; Epigenesis, Genetic; 3. Good health; Pancreatic Neoplasms; 03 medical and health sciences; Mutation; Humans; Genes, Tumor Suppressor; Carcinoma, Pancreatic Ductal

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 deletions, mutational signatures suggesting defective repair. In contrast pancreatic ductal adenocarcinoma, no recurrent point mutations are detected. suppressors ID3, ARID1A, APC, CDKN2A impaired also on the protein level thus potentially affect ACC tumorigenesis. Consequently, this work identifies promising therapeutic in drugs recently approved precision cancer therapy.