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New Study Sheds Light on Role of APOBEC3 in Mutagenesis

New details about the mechanism by which the APOBEC3 family of cytosine deaminases drive mutagenesis in human cancer cells are presented in this week's Nature. APOBEC3 has been implicated in some of the most prevalent mutational signatures in cancer, yet a causal link between endogenous APOBEC3 enzymes and mutational signatures in human cancer genomes has not been established, leaving the mechanisms of APOBEC3 mutagenesis poorly understood. To investigate mechanisms of APOBEC3 mutagenesis, a team led by researchers from the Broad Institute and Memorial Sloan Kettering deleted candidate APOBEC3 mutators from human cancer cell lines that generate the relevant mutations naturally over time. Analyzing non-clustered and clustered signatures across whole-genome sequences from 251 breast, bladder, and lymphoma cancer cell line clones reveals that deletion of the APOBEC3A enzyme diminished APOBEC3-associated mutational signatures. Other findings include the decrease, but not elimination, of APOBEC3 mutation burdens through the deletion of APOBEC3A and APOBEC3B. Overall, the findings represent "causal evidence for the hypothesis put forward two decades ago that APOBEC3 enzymes can act as endogenous sources of mutation in cancer.

The Scan

ChatGPT Does As Well As Humans Answering Genetics Questions, Study Finds

Researchers in the European Journal of Human Genetics had ChatGPT answer genetics-related questions, finding it was about 68 percent accurate, but sometimes gave different answers to the same question.

Sequencing Analysis Examines Gene Regulatory Networks of Honeybee Soldier, Forager Brains

Researchers in Nature Ecology & Evolution find structural network differences between soldiers and foragers, suggesting bees can take on either role.

Analysis of Ashkenazi Jewish Cohort Uncovers New Genetic Loci Linked to Alzheimer's Disease

The study in Alzheimer's & Dementia highlighted known genes, but also novel ones with biological ties to Alzheimer's disease.

Tara Pacific Expedition Project Team Finds High Diversity Within Coral Reef Microbiome

In papers appearing in Nature Communications and elsewhere, the team reports on findings from the two-year excursion examining coral reefs.