AID/APOBEC deaminases and cancer
Stefan Rebhandl1,2, Michael Huemer1,2, Richard Greil1,2, Roland Geisberger1,2
1 Department of internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectious Diseases, Rheumatology, Oncologic Center, Laboratory for Immunological and Molecular Cancer Research, Paracelsus Medical University Salzburg, Austria
2 Salzburg Cancer Research Institute, Salzburg, Austria
Correspondence:
Roland Geisberger, email:
Keywords: deamination, cancer, AID, APOBEC3, mutation signature, mutation cluster, kataegis
Received: February 19, 2015 Accepted: March 16, 2015 Published: April 28, 2015
Abstract
Mutations are the basis for evolution and the development of genetic diseases. Especially in cancer, somatic mutations in oncogenes and tumor suppressor genes alongside the occurrence of passenger mutations have been observed by recent deep-sequencing approaches. While mutations have long been considered random events induced by DNA-replication errors or by DNA damaging agents, genome sequencing led to the discovery of non-random mutation signatures in many human cancer. Common non-random mutations comprise DNA strand-biased mutation showers and mutations restricted to certain DNA motifs, which recently have become attributed to the activity of the AID/APOBEC family of DNA deaminases. Hence, APOBEC enzymes, which have evolved as key players in natural and adaptive immunity, have been proposed to contribute to cancer development and clonal evolution of cancer by inducing collateral genomic damage due to their DNA deaminating activity. This review focuses on how mutagenic events through AID/APOBEC deaminases may contribute to cancer development.
