Oncogene Variations Are Common in Endstage Dilated Cardiomyopathies

Background: Heart failure patients are at increased risk for developing newly diagnosed cancer. The epidemiology of this increased risk is poorly understood. Treatment strategies, chronic inflammation and shared genetic triggers are potential mechanisms. Our objective was to assess the prevalence of damaging oncogene mutations in non-ischemic cardiomyopathy patients undergoing LVAD placement. Methods: Explanted human heart tissue procured at the time of LVAD placement was obtained from the heart tissue bank at the University of Nebraska. Cancer associated genes were sequenced utilizing an inherited disease panel (Ion Torrent). Genomic DNAwas isolated from tissues using the All DNA/RNA mini kit (Qiagen). 10 ng of DNAwas amplified by PCR using inherited diseases panel primer pools. The amplicons were then ligated to adapters and additional library amplification was done by emulsion PCR on Ion Sphere particles (ISPs). Sequencing was performed on PGM sequencer (Ion torrent) using the Ion 316 chip. The Ion Torrent browser suite was used to map the reads and call the variants. The identified single nucleotide polymorphisms, insertions, and deletions were then annotated and characterized with ANNOVAR. Variants with a population frequency of less than or equal to 1% were identified and analyzed utilizing an open source integrative genomics viewer. Amino acid substitution effects on protein function were determined by a bioinformatics algorithm (MutationTaster program). Results: Our sample population included 6 males and 2 females with an average age of 57 and an average EF at presentation of 18%. All of our samples contained oncogene variants. Notably, all samples had the same ATM variant. Conclusion: Rare oncogenes variants are highly prevalent in the advanced heart failure population. The higher frequency of cancer in heart failure populations may be attributable to a higher frequency of variant cancer genes. These results also suggest that altered DNA repair mechanisms may be essential to the progression and worsening of advanced heart failure.