AI Article Synopsis
- Many genes linked to acute myeloid leukemia (AML) are only mutated in a small number of patients, showing that other ways to disrupt genes might be involved.
- Researchers discovered changes in how certain genes are spliced (or cut) that affect gene activity in more AML patients than just the known mutations.
- They also found that a specific factor, DHX34, is spliced in a way that creates a problem similar to inherited mutations seen in families with AML, proving that just looking for mutations isn't enough to understand the disease.
Article Abstract
Most genes associated with acute myeloid leukemia (AML) are mutated in less than 10% of patients, suggesting that alternative mechanisms of gene disruption contribute to this disease. Here, we find a set of splicing events that alter the expression of a subset of AML-associated genes independent of known somatic mutations. In particular, aberrant splicing triples the number of patients with reduced functional EZH2 compared with that predicted by somatic mutation alone. In addition, we unexpectedly find that the nonsense-mediated decay factor DHX34 exhibits widespread alternative splicing in sporadic AML, resulting in a premature stop codon that phenocopies the loss-of-function germline mutations observed in familial AML. Together, these results demonstrate that classical mutation analysis underestimates the burden of functional gene disruption in AML and highlight the importance of assessing the contribution of alternative splicing to gene dysregulation in human disease.
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Source |
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054020 | PMC |
| http://dx.doi.org/10.1073/pnas.2014967118 | DOI Listing |
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