MLH1 and neoplasm: For example, tumours driven by the RET M918T variant were predominantly of the mesenchymal subtype, with prevalent upregulation of extracellular matrix pathways, frequent epigenetic DNA methylation and the poorest prognosis, whereas RAS-driven tumours were more likely to be of the metabolic subtype, with upregulation of pathways related to cellular metabolism, higher frequency of somatic copy number alterations (CHEK2, MUTYH, TP53, ATM, MLH1), strong activation of the MAPK and PI3K pathways, and associated with an intermediate prognosis [28].