102 From the 1 Genetics, Cell Biology, and Development Department, University of Minnesota, Minneapolis, MN, USA; 2 Evolution, Ecology, and Behavior Department, University of Minnesota, Minneapolis, MN, USA; 3 Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; 4 Institute for Molecular Virology, University of Minnesota, Minneapolis, MN, USA; 5 Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA; 6 Microbiology, Cancer Biology and Immunology Graduate Program, University of Minnesota, Minneapolis, MN, USA; 7 Biochemistry, Molecular Biology and Biophysics Department, University of Minnesota, Minneapolis, MN, USA Received: Jul. 09, 2014; Accepted: Nov. 26, 2014 Correspondence to: Prof. Reuben S. Harris, University of Minnesota, Biochemistry, Molecular Biology and Biophysics Department. 321 Church Street S.E., 6‑155 Jackson Hall, Minneapolis, Minnestoa, 55455 USA. Tel: 1‑612‑6240457; Fax: 1‑612‑6252163; Email: rsh@umn.edu DOI: 10.4103/2319‑4170.148904 Cancer is a disease that results from alterations in the cellular ge‑ nome. Several recent studies have identified mutational signatures that implicate a variety of mutagenic processes in cancer, a major one of which is explained by the enzymatic activity of the DNA cytosine de‑ aminase, APOBEC3B. As a deaminase, APOBEC3B converts cytosines to uracils in single‑stranded DNA. Failure to properly repair these uracil lesions can result in a diverse array of mutations. For instance, DNA uracils can template the insertion of complementary adenines leading to C‑to‑T transition mutations. DNA uracils can also be converted into abasic sites that, depending upon the DNA polymerase recruited to by‑ pass this lesion in the template strand, can lead to adenine insertion and C‑to‑T mutations as well as cytosine insertion and C‑to‑G transversion mutations. Finally, DNA uracils can also be converted into DNA breaks that may precipitate some types of larger chromosomal aberrations observed in cancer. These stud‑ ies cumulatively demonstrate that APOBEC3B is a major source of genetic heterogeneity in several human cancers and, as such, this enzyme may prove to be a critical diagnostic and therapeutic target. (Biomed J 2015;38:102-110) Key words: APOBEC3B, cancer, DNA cytosine deamination, genomic uracil, mutation C ancer is a genetic disease. For a malignancy to form and evolve, it needs to override the normal cellular safeguards encoded by the genome. Therefore, to prevent cancer initiation and limit its malignant potential, it is vital to understand the different sources of DNA damage and mutation that underlie this disease. [1] Tumor genomes bear mutational signatures that reflect the underlying sources of those mutations. For instance, a mutation spectrum result‑ ing from a combination of oxidative damage and a defect in DNA mismatch repair (MMR) will look different than a mutation signature resulting from oxidative damage alone. Research is underway to quantitatively deconvolute the multiple sources that give rise to these complex mutation patterns. [2‑4] The sources of DNA damage and mutation in cancer can be classified into the general categories of exogenous and endogenous, where the exogenous sources are those that arise from the environment and the endogenous sources are those that arise from within the cell itself. Pyrimidine dimers that result from UV damage are a classic example of an exogenous agent generating lesions that lead predominantly to context‑specific C‑to‑T transition mutations. [5,6] Endogenous processes can be fur‑ ther categorized into passive and active sources of DNA damage and mutation. Passive mutation is characterized by a failure to repair DNA damage after it has occurred. Established sources of passive mutation are inherited de‑ ficiencies in DNA repair processes, such as MMR gene defects that are characterized molecularly by microsatel‑ lite DNA instability and clinically by predisposition to hereditary nonpolyposis colorectal cancer (HNPCC). APOBEC3B: Pathological Consequences of an Innate Immune DNA Mutator Michael B. Burns 1,2,3 , Brandon Leonard 3,4,5,6 , Reuben S. Harris 3,4,5,7 Prof. Reuben S. Harris Special Edition