Clinical Genetics in Cardio-Oncology

Damaging genetic variants in cancer and cardiac genes are common in end-stage non-ischemic cardiomyopathy patients. Heart failure patients are at higher risk for developing newly diagnosed cancer. There is also a significant chance of developing cardiomyopathy after receiving chemotherapy treatment for cancer. Our objective was to assess the frequency of damaging oncogene and cardiac gene mutations in cancer and cardiomyopathy patients by using next generation sequencing (NGS). Genomic DNA from blood of 4 groups of patients were used from the Nebraska Biobank The first group included only cardiomyopathy, second group included breast or lymphoma cancer only, the third group included healthy as a control and the fourth group included both cardiomyopathy and cancer patients. Individual libraries were amplified by emulsion PCR on Ion Sphere particles and sequencing was performed on a PGM sequencer. 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. Non-synonymous mutations with a population frequency of less than or equal to 1% were identified and analyzed. Amino acid substitutions on protein function were determined by a bioinformatics algorithm. Our sample population included 29 females and 4 males with an average age of 61 and had 82% Caucasian, 15% African American and 3% Asian. Table showed the occurrence of damaging variants of cardiac and cancer genes in four different groups. NGS is very efficient way of identifying pathogenic mutations. Damaging variants in cardiomyopathy genes are common in the dilated cardiomyopathy patients. Damaging variants in oncogenes are also common in cancer patients as expected relative to controls. Cancer patients who develop cardiomyopathy have a higher prevalence of damaged cardiomyopathy genes. These genetic variations could be utilized to identify cancer patients at higher risk of developing chemotherapy induced cardiomyopathy.Tabled 1PatientsCardiac Mutations/patients noOncogene Mutations/patients noCardiomyopathy8/102/10Cancer2/95/9Control1/102/10Cardiomyopathy + Cancer4/43/4 Open table in a new tab