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The four mismatch repair proteins proofread newly copied DNA; when a tumour loses one of them its DNA fills with small errors, and that state (dMMR or MSI-high) is what lets immunotherapy work across many cancers. This dossier gathers the 0 products (0 approved), 0 trials, 0 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Deficient repair raises the mutation rate a hundredfold and produces frameshift neoantigens in repeat-containing genes, which is the mechanistic basis for checkpoint inhibitor sensitivity.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Colorectal cancer | 5-15% | Microsatellite instability or mismatch repair deficiency | Stage matters more than anything else. In unselected surgical series: 38 of 276, 13.8%, MSI-high in the TCGA cohort with a further 44 MSI-low (Cancer Genome Atlas Network 2012); 91 of 529, 17.2%, in the 619-exome prospective cohort (Giannakis 2016); 770 of 7,217, 10.7%, in crc_msk_2026, which splits into 710 of 5,138 primaries (13.8%) and 59 of 2,045 metastases (2.9%); 125 of 1,513, 8.3%, in crc_eo_2020; 76 of 1,015, 7.5%, in crc_sysucc_2022 (cBioPortal). In first-line metastatic trial populations it collapses: 153 of 3,063, 5.0%, pooled across CAIRO, CAIRO2, COIN and FOCUS (Venderbosch 2014) and 18 of 515, 3.5%, in a phase 3 advanced cohort, 13 of them from MLH1 promoter hypermethylation (Koopman 2009). | doi.org |
| Gallbladder cancer | 0.6-2.5% | Microsatellite instability (MSI-high) | 6 of 244 samples, 2.5%, called unstable by MSIsensor in cBioPortal gbc_mskcc_2022; 0.6% (2 of 170 tested) in Indian patients (Suryavanshi 2025); 1.3% (4 of 308) in Western cholangiocarcinoma by mononucleotide markers (Goeppert 2019); gallbladder and intrahepatic tumours carried more MSI-high, PD-L1 and TMB-high than extrahepatic (Weinberg 2019). | cBioPortal (TCGA) |
| Pancreatic ductal adenocarcinoma | 0.5-2% | Mismatch repair deficiency or microsatellite instability | 7 of 833, 0.8%, all with Lynch syndrome, 4 of 7 benefiting from checkpoint blockade (Hu 2018, Clin Cancer Res); MSI-high and/or TMB-high in 0.5% of 2,563 assessed (Singhi 2019); 1 to 2% across 34 studies and 8,323 patients, associated with medullary and colloid histology and KRAS/TP53 wild-type background (Luchini 2021); 4.7% of KRAS wild-type against 0.7% of KRAS-mutant tumours (Philip 2022); cBioPortal: MSI_TYPE unstable in 6 of 1,119 reported samples and MSIsensor score 10 or more in 10 of 2,314 in pdac_msk_2024; 2 of 323 reported in pancreas_msk_2024; no TCGA sample reached MANTIS 0.4. Germline MLH1 0.13% of 3,030, odds ratio 6.66 (Hu 2018, JAMA). | doi.org |
| Triple-negative breast cancer | 0-2% | Microsatellite instability or mismatch repair deficiency | No MSI-high tumour among 195 by PCR and one mismatch-repair-deficient tumour (lost MSH2) among 440 by IHC in Chinese TNBC (Ren 2021); 2 of 228 Japanese TNBCs MSI-high, 0.9% (Kurata 2020); about 4.7% of HRDetect-low tumours, roughly 1.7% of all 237 whole genomes, mismatch-repair deficient (Staaf 2019); cBioPortal: MSIsensor score 10 or more in 3 of 122 triple-negative exomes in brca_tcga_pan_can_atlas_2018, an algorithmic call not confirmed by PCR. | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
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Query for this target: (TITLE:"Mismatch repair proteins" OR ABSTRACT:"Mismatch repair proteins" OR TITLE:"MLH1, MSH2, MSH6, PMS2" OR ABSTRACT:"MLH1, MSH2, MSH6, PMS2" OR TITLE:"MLH1" OR ABSTRACT:"MLH1" OR TITLE:"MSH2" OR ABSTRACT:"MSH2" OR TITLE:"MSH6" OR ABSTRACT:"MSH6" OR TITLE:"PMS2" OR ABSTRACT:"PMS2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/mmr.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/mmr.json. Licence CC BY-NC 4.0.