Hereditary Fusion Genes Are Associated with the Inheritance of Acute Myeloid Leukemia

Abstract

ABSTRACTFusion genes are 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 curated HFGs to analyze AML fusion genes, and we identified 243 HFGs associated with AML inheritance from 926 potential HFGs. Many HFGs were one-to-many and many-to-one fusions that augmented signals from environmental and genomic alterations and seemed to support the “two-hit” hypothesis. The most highly-recurrent HFGs were also observed in multiple myeloma and monozygotic twin datasets, suggesting that AML is a complex genetic disease. HFGs, as cancer genetic biomarkers, are the most basic foundations for future genetic and genomic studies.