Other markers of the immune microenvironment include the tumour mutation load, which is reported as being ‘high’ in 11.8% of patients, and microsatellite instability, which is ‘high’ in 1.8% of patients with CUP.56 Mutations in MLH1 (mutL homologue 1), a DNA mismatch repair protein, have been detected in 1.6% of patients with CUP using circulating tumour DNA.66 MSI (microsatellite instability) is associated with a high tumour mutational burden and is a predictive biomarker of response to immune checkpoint inhibitors in a multitude of tumours. The gene discussed is MLH1; the disease is neoplasm.