Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target.

ABSTRACT: The genomic landscape of colorectal cancer (CRC) is shaped by inactivating mutations in tumour suppressors such as APC, and oncogenic mutations such as mutant KRAS. Here we used genetically engineered mouse models, and multimodal mass spectrometry-based metabolomics to study the impact of common genetic drivers of CRC on the metabolic landscape of the intestine. We show that untargeted metabolic profiling can be applied to stratify intestinal tissues according to underlying genetic alterations, and use mass spectrometry imaging to identify tumour, stromal and normal adjacent tissues. By identifying ions that drive variation between normal and transformed tissues, we found dysregulation of the methionine cycle to be a hallmark of APC-deficient CRC. Loss of Apc in the mouse intestine was fou

SUBMITTER: Vande Voorde J 

PROVIDER: S-EPMC10447251 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature