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Enzyme Involved in Lipid Metabolism Linked to Mutational Signatures

An enzyme involved in nutrient absorption in the small intestine appears to play a role in two mutational signatures found in many different cancers, according to a study appearing in Nature Genetics this week. APOBEC is a family of enzymes that edit DNA or RNA and play a role in immunity. Previous research has shown that two APOBEC-related mutational signatures — SBS2 and SBS13 — are common to different human cancers, but little is known about their causes or the APOBEC enzymes involved. In this week's study, a team led by Wellcome Sanger Institute scientists whole-genome sequenced 342 normal epithelial crypts from the small intestines of 39 individuals and found that SBS2 and SBS13 mutational signatures were fairly common despite being rare in the large intestine and most other normal tissues. Similarly, they found that levels of APOBEC1 — an APOBEC family member functions controls lipid metabolism in the intestine by mediating apolipoprotein B (APOB) mRNA editing — were much higher in the small intestine epithelium versus other tissues. "The results suggest that the high levels of SBS2/SBS13 in the small intestine are collateral damage from APOBEC1 fulfilling its physiological function of editing APOB mRNA," the study's authors write.