ArticleJCO precision oncology2024
Genomic Alterations in DNA Mismatch Repair Genes Across Different Cancer Types.
Article in JCO precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Trastuzumab deruxtecan in HER2-expressing gynecologic cancers from DESTINY-PanTumor02: antitumor activity, safety, and exploratory biomarker analyses.Journal of gynecologic oncology · 2026Trial
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12 authors.
Funding
Abstract
purposePD-1 inhibition is effective in patients with mismatch repair deficient (dMMR) solid tumors in a tumor-agnostic fashion. However, dMMR testing by immunohistochemistry (IHC) is not routinely performed across tumor types. By contrast, next-generation sequencing (NGS) for somatic genomic alterations is frequently performed across tumor types. We hypothesized that NGS would identify patients with alterations in mismatch repair (MMR) genes and that these patients would have higher rates of MMR protein loss by IHC. This would support the utility of IHC reflex testing after NGS and potential matching to approved therapeutic options.
methodsFrom January 2016 to December 2021, 15,701 patients with solid tumors received NGS covering the MMR genes, and 4,994 patients had both IHC and NGS. Sequencing results were analyzed for mutations in MMR genes, tumor type distribution, and concordance with IHC results when available.
resultsSix hundred and ninety-eight (4.4%) of 15,701 patients had mutations in one of the MMR genes. Mutations were found across tumor types. Three hundred and seventeen (6.3%) of 4,994 patients displayed IHC loss for at least one MMR protein. 33.8% patients (110/325) patients with MMR mutations had dMMR, compared with just 4.4% (207/4,669) patients without mutations (
conclusionMutations in MMR genes are found in multiple tumor types where IHC testing is not routine. Reflex IHC testing of patients carrying MMR gene mutations, especially those known or inferred to be inactivating, may identify more patients with dMMR and matched treatment options. However, dedicated IHC screening is needed to capture majority of the patients.
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