Other results were also somewhat surprising. Researchers knew that mutations in signaling genes, which help control cell growth and development, were very common in AML, and thought that all AML samples may have at least one signaling gene mutation. But the TCGA findings showed that these genes are mutated in only 60 percent of cases. These include mutations in the gene FLT3, which occur in about a third of cases, making it one of the most commonly mutated genes in AML. FLT3 is important for normal blood cell development. The researchers also found that many AML patients have concurrent mutations in three commonly mutated genes: FLT3, NPM1 and DNMT3A. Patients with this combination of gene mutations appear to have a unique subtype of AML.
Investigators unexpectedly found recurring mutations in cohesin genes, which are important in cell division.
The study is the first to report a recurrently mutated microRNA gene in AML. MicroRNAs can play an important role in regulating gene expression, particularly in turning off gene activity.
Abnormal chromosome rearrangements and gene fusions (where two genes join to form a new, altered gene) are frequently useful in diagnosing and providing prognostic information for AML patients. The study uncovered many such fusions that had not been described before, and nearly half of the AML samples were found to have gene fusions.
Currently, only a few good markers exist to help guide treatment decisions for the majority of patients with intermediate risk. Some of the recurrently mutated genes identified in this study may allow for better prognostic information that will be relevant for AML patients.
"We've never had such a complete picture of AML, and this data set will be mined by researchers for years," said co-study leader Richard Wilson, Ph.D., director of Washington University's Genome Institute. "These findings have probably identi
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NIH/National Cancer Institute