The APOBEC3 cytidine deaminases produce two of the most prevalent mutational signatures in human cancer. APOBEC3A drives most of this ongoing mutagenesis, despite being almost undetectable in bulk measurements of tumors.
We resolved part of that contradiction by showing the enzyme acts in bursts, switching on within a rare and short-lived cell state resembling squamous differentiation, and that cancer drugs can push cells into the same state. We are defining what controls entry into it and what a single passage costs the genome.
Read more at maciejowskilab.org.
