Research reveals cancer threat from virus protecting enzymes

According to a study led by Weill Cornell Medicine researchers, an enzyme that protects human cells from viruses may contribute to cancer progression into a more malignant state by inducing a variety of mutations in cancer cells.

The discovery suggests that the enzyme could be used as a target for future cancer therapies. The researchers used a preclinical model of bladder cancer to investigate the role of the enzyme APOBEC3G in promoting the disease and discovered that it significantly increased the number of mutations in tumour cells, increasing the genetic diversity of bladder tumours and hastening mortality.

"Our findings suggest that APOBEC3G is a big contributor to bladder cancer evolution and should be considered as a target for future treatment strategies," said study senior author Dr. Bishoy M. Faltas, assistant professor of cell and developmental biology at Weill Cornell Medicine, and an oncologist who specializes in urothelial cancers at NewYork-Presbyterian/Weill Cornell Medical Center.

The APOBEC3 family of enzymes is capable of mutating RNA or DNA--by chemically modifying a cytosine nucleotide (letter "C" in the genetic code). This can result in an erroneous nucleotide at that position.

Identifying the specific mutational signature of APOBEC3G and mapping it in the tumour genomes, the team found ample evidence that the enzyme had caused a greater mutational burden and genomic diversity in the tumours, likely accounting for the greater malignancy and mortality in the APOBEC3G mice, distinct mutational signature caused by APOBEC3G in these tumours that is different from signatures caused by other members of the APOBEC3 family.

Lastly, the researchers looked for APOBEC3G's mutational signature in a widely used human tumour DNA database, The Cancer Genome Atlas, and found that these mutations appear to be common in bladder cancers and are linked to worse outcomes.