Immunity Proteins Linked to Cancer

A set of proteins involved in immunity, which are supposed to defend the body, have the adverse effect of creating a large number of mutations in DNA.

These genetic mutations produce tumors in the human body, especially when these proteins transform, and can account for the majority of variations in some very aggressive cancers.

Scientists from the US National Institute of Environmental Health Sciences (Durham, NC, USA) examined 954,247 mutations within 2,680 cancer samples. Almost 70% of mutations resulted from the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like cytidine deaminases (APOBEC) protein in some tumors. The investigators found that APOBEC mutations can outnumber all other mutations in some cancers, accounting for over two-thirds in some bladder, cervical, breast, head and neck, and lung tumors.

The APOBEC proteins are known to be of benefit, shutting down viruses that attack the body, but the scientists were surprised to find that they are also a detriment, mutating DNA. They found 498 total clusters in the 2,680 sequenced exomes from 14 different cancer types. In total, 218 cytosine- or guanine-coordinated clusters were identified, occurring in every cancer type analyzed except acute myeloid leukemia. Several cancer types showed high levels of the APOBEC mutation pattern as well as a wide variation among individual samples, which could reflect different biological pathways leading to carcinogenesis and the greatest range of variation was observed in breast cancer.

Dmitry A. Gordenin, PhD, a senior scientist and corresponding author of the study 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.” His coauthor, Steven A. Roberts, added, “We hope that determining the environmental link to these mutations will lead to viable cancer prevention strategies.” The study was published on July 14, 2013, in the journal Nature Genetics.

Related Links:
US National Institute of Environmental Health Sciences