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Endometrial and acute myeloid leukemia cancer genomes characterized
Date:5/1/2013

genome sequencing, which is an examination of the complete DNA blueprint of the cells. Researchers analyzed the genome's protein-coding regions in the remaining samples, and used powerful new sequencing methods to look at changes in RNA in each case.

By studying a large number of AML cases, investigators were able to predict that they have identified virtually all of the mutations that occur in at least 5 percent of AML patients. Surprisingly, they found that overall, AML genomes have relatively few mutations, and such tumors are among the least mutated adult cancers. The average number of mutations in genes for each AML genome was 13, in contrast to solid tumors such as breast, lung or pancreatic cancer, which often have hundreds of mutated genes.

Because investigators found more than 1,600 genes that were mutated at least once in the 200 samples, they organized the recurrently mutated genes into nine categories based on their function or the known pathways involved. Some of these categories include tumor suppressor genes, signaling genes and epigenetic modifiers, with the latter being the most frequently mutated class of genes in the study. Epigenetic changes are alterations to DNA that often involve the addition or removal of chemical tags (such as methyl groups), which can affect when genes are turned on and off.

"This data set helps to integrate what was previously fragmented information," said study co-leader Timothy J. Ley, M.D., associate director for cancer genomics at The Genome Institute at Washington University School of Medicine in St. Louis. "We didn't realize how few recurrent mutations there were, and no one was thinking even five years ago that AML was associated with a high frequency of mutations in genes that encode epigenetic modifiers."

By finding comparatively few recurrently mutated genes, yet frequent alterations in genes that help control gene expression, the investigators may have narrowed the search fo
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