Researchers have identified a set of proteins involved in immunity that produce mutations in the body’s DNA which can potentially cause cancer. The finding was published in the journal Nature Genetics.
The proteins belong to a group called apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) cytidine deaminases. The investigators found that APOBEC mutations are responsible for a large percentage of cancer tumors. The study is a follow up of
Their earlier study found mutation clusters with analogous features in sequenced human cancers and that “clustered mutations in cancers occur at motifs of cytosine deamination by APOBECs.”
Dmitry Gordenin, Ph.D, senior associate scientist at the National Institute of Environmental Health Sciences (NIEHS) was the corresponding author of the paper.
He said his research team, headed by Michael Resnick, Ph.D., was surprised to find that APOBEC was capable of mutating human DNA, considering it has an essential role in inactivating viruses that attack the body.
Gordenin said “the presence of APOBEC clusters in the genome of tumor cells indicates that APOBEC enzymes could also have caused many mutations across the genome.”
The team, which included Gad Getz, Ph.D., and other colleagues at the Broad Institute of MIT and Harvard University, analyzed the number of genome-wide APOBEC mutageneses that were listed in the NIH’s cancer database “The Cancer Genome Atlas”.
They identified around a million APOBEC mutations in only 2,680 cancer samples. In some cases up to 70 percent of mutations in the tumors were due to APOBEC mutagenesis.
The first author of the study, Steven Roberts, Ph.D., said that because of APOBECs importance in regulating the immune system, it is very responsive to environmental factors. He said the team hopes “that determining the environmental link to these mutations will lead to viable cancer prevention strategies.”