In Nature this week, scientists from the University of Minnesota report on the identification of a likely source of genetic mutations required for cancer development. The team specifically found that the DNA cytosine deaminase APOBEC3B is upregulated in most primary breast tumors and breast cancer cell lines. "Tumors that express high levels of APOBEC3B have twice as many mutations as those that express low levels and are more likely to have mutations in TP53," they write. Knockdown experiments also show that endogenous APOBEC3B correlates with increased levels of genomic uracil, increased mutation frequencies, and the C-to-T transitions found in many cancer types. Additionally, induced APOBEC3B over-expression triggers cell cycle deviations, cell death, DNA fragmentation, gamma-H2AX accumulation, and C-to-T mutations.
Meanwhile, in this week's Nature Genetics, researchers from the NYU Cancer Institute describe the discovery of a mutation that contributes to the drug resistance of acute lymphoblastic leukemia in children. Although cure rates for the disease are high, an estimated 10 percent to 20 percent of patients experience a relapse caused by the disease's resistance to treatment. Transcriptome RNA sequencing of bone marrow samples from 10 relapsed ALL patients revealed specific mutations in cytosolic 5'-nucleotidase II gene in two patients as well as in 61 additional relapse specimens, suggesting a genetic basis for drug-resistant ALL.