Researchers at the University of Minnesota have discovered that a human antiviral enzyme causes DNA mutations that lead to several forms of cancer.
The discovery, reported in the July 14 issue of Nature Genetics, follows the team's earlier finding that the enzyme, called APOBEC3B, is responsible for more than half of breast cancer cases. The previous study was published in Nature in February.
APOBEC3B is part of a family of antiviral proteins that Harris has studied for more than a decade. His effort to understand how these proteins work has led to these surprising discoveries that APOBEC3B is a broadly important cancer mutagen.
"We are very excited about this discovery because it indicates that a single enzyme is one of the largest known contributors to cancer mutation, possibly even eclipsing sources such as UV rays from the sun and chemicals from smoking," says Reuben Harris, a professor of biochemistry, molecular biology and biophysics based in the College of Biological Sciences. Harris, who led the study, is also a member of the Masonic Cancer Center, University of Minnesota.
For the current study, Harris, along with colleagues Michael Burns and Alpay Temiz, analyzed tumor samples from 19 different types of cancer for the presence of APOBEC3B and 10 related proteins. Results showed that APOBEC3B alone was significantly elevated in six types (bladder, cervix, two forms of lung cancer, head & neck, and breast). Levels of the enzyme, which is present in low levels in most healthy tissues, were elevated in several other types of cancer as well.
A second key finding was that the mutational signature of APOBEC3B is a close match to the actual mutation pattern in these cancers. "Much like we each have unique written signatures, these enzymes each leave a unique mark," Harris says.
Findings from both studies are counterintuitive because the enzyme, which is produced by the immune system, is supposed to p
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University of Minnesota