TY - JOUR T1 - Alternative splicing redefines landscape of commonly mutated genes in acute myeloid leukemia JF - bioRxiv DO - 10.1101/2020.05.21.107557 SP - 2020.05.21.107557 AU - Osvaldo D. Rivera AU - Michael J. Mallory AU - Mathieu Quesnel-Vallières AU - David C. Schultz AU - Martin Carroll AU - Yoseph Barash AU - Sara Cherry AU - Kristen W. Lynch Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/05/22/2020.05.21.107557.abstract N2 - Most genes associated with Acute Myeloid Leukemia (AML) are mutated in less than 10% of patients, suggesting alternative mechanisms for gene disruption contribute to this disease. Here we find a set of splicing events that disrupt the expression of a subset of AML-associated genes, including EZH2 and ZRSR2, independent of known somatic mutations. Most strikingly, in at least one cohort, aberrant splicing triples the number of patients with a reduction in functional EZH2 as compared to that predicted by somatic mutation of EZH2 alone. Together, these results demonstrate that classical mutation analysis underestimates the burden of functional gene disruption in AML and highlights the importance of assessing the contribution of alternative splicing to gene dysregulation in human disease.Competing Interest StatementThe authors have declared no competing interest. ER -