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The Hereditary Fusion Genes are Associated with the Inheritance of Acute Myeloid Leukemia

Ling Fei, Jinfeng Yang, Noah Zhuo, Degen Zhuo

Fusion genes had been thought to be somatic and cause cancer, including Acute Myeloid Leukemia (AML). Validating highly-recurrent fusion genes in healthy samples compelled us to systematically study Hereditary Fusion Genes (HFGs). Here, we used the previously-curated 1180 HFGs from Monozygotic (MZ) twins to analyze total fusion transcripts from AML patients and identified 926 (78.5%) HFGs overlapped with AML. We selected 242 HFGs ranging from 10% to 83.3% to perform comparative analysis and showed that 239 HFGs were significantly higher than their counterparts of Genotype-Tissue Expression (GTEx) blood samples and associated with AML inheritances. A 5’-gene and 3’-gene were fused with multiple 3’-genes and 5’-genes, respectively, to form biological networks and result in potential hyper susceptibility to somatic genetic and environmental abnormalities. Many highly-recurrent HFGs were also observed in Multiple Myeloma (MM) and MZ twins, suggesting that complex traits and diseases shared common hereditary factors. This study shed the first light on HFGs as most “inherited” genetic factors and provided potential therapeutic targets, leading to paradigm shifts in cancer and disease diagnosis and research