CIMP-high tumours, frequent in the C1 cluster, are characterised by CpG islands hypermethylation in the promoter regions of multiple genes, leading to reduced expression of several genes associated with lung cancer development and prognosis, such as CLDN18, ANK1 and PTPRCAP. Potential therapeutic approaches for CIMP-high tumours include DNA demethylating agents and histone deacetylase inhibitors, though their efficacy in lung cancer remains unproven. The gene discussed is CLDN18; the disease is lung cancer.