ArticleJournal for immunotherapy of cancer2020
Complete response to anti-PD-L1 antibody in a metastatic bladder cancer associated with novel MSH4 mutation and microsatellite instability.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 60 citations in OpenAlex.
- Emerging role of DNA polymerase epsilon non-exonuclease domain mutations in colorectal cancer: From sequence variants to clinical implications.World journal of gastroenterology · 2026Article
- Machine Learning in Biomarker-Driven Precision Oncology: Automated Immunohistochemistry Scoring and Emerging Directions in Genitourinary Cancers.Current oncology (Toronto, Ont.) · 2026Review
- Complete response to pembrolizumab in mismatch repair-deficient urothelial carcinoma with local recurrence and recurrent upper tract urothelial carcinoma: a case report.International cancer conference journal · 2025Article
- Independent prognostic value of CLDN6 in bladder cancer based on M2 macrophages related signature.iScience · 2024Article
- Mismatch repair deficiency and microsatellite instability in urothelial carcinoma: a systematic review and meta-analysis.BMJ oncology · 2024Article
- Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer.Genome biology · 2023Article
- Multi-omic analysis in normal colon organoids highlights MSH4 as a novel marker of defective mismatch repair in Lynch syndrome and microsatellite instability.Cancer medicine · 2023Article
- Novel CandidateCancers · 2023Article
- Clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in Chinese population with mismatch repair deficient urothelial carcinoma: a real-world study.Frontiers in immunology · 2023Article
- Response to Immune Checkpoint Inhibitors Is Affected by Deregulations in the Antigen Presentation Machinery: A Systematic Review and Meta-Analysis.Journal of clinical medicine · 2022Review
- Looking beyond the cytogenetics in haematological malignancies: decoding the role of tandem repeats in DNA repair genes.Molecular biology reports · 2022Article
- Programmed Cell Death-Ligand-1 expression in Bladder Schistosomal Squamous Cell Carcinoma -Frontiers in immunology · 2022Review
- Discovery of core gene families associated with liver metastasis in colorectal cancer and regulatory roles in tumor cell immune infiltration.Translational oncology · 2021Article
- Activation of the DDR Pathway Leads to the Down-Regulation of the TGFβ Pathway and a Better Response to ICIs in Patients With Metastatic Urothelial Carcinoma.Frontiers in immunology · 2021Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMicrosatellite instability (MSI) occurs in 3% of urothelial carcinomas as a result of germline or somatic loss of function mutation in mismatch repair (MMR) proteins.1 Although MSH4 is a member of the DNA MMR mutS family, the association of MSH4 mutation with MSI has not been described. We report a complete responder to PD-L1 blockade who had MSH4 mutated metastatic bladder cancer with mixed histology and MSI. The genomics of urothelial, plasmacytoid and squamous histology was characterized individually through microdissection. CASE PRESENTATION: An 81-year-old man was diagnosed with metastatic urothelial carcinoma 8 months after a cystectomy for muscle invasive bladder cancer. His disease was primary refractory to first-line platinum-based chemotherapy but attained complete response to second-line atezolizumab. PCR-based assay revealed MSI high. The tumor mutational burden was elevated to 36.7 mut/Mb. However, immunohistochemistry of MLH1, MSH2, MSH6 and PMS2 was intact. Whole exome sequencing confirmed that the above mentioned four classic MMR genes were wild type but revealed a deleterious MSH4 L359I mutation with variant allele fraction of 30% and Polyphen2 score of 0.873. The association of MSH4 alterations and MSI-H was independently verified in two publicly available MSI-H colorectal cancer datasets.
conclusionsThe novel MSH4 L359I mutation is associated with MSI and high mutational burden leading to remarkable response to PD-L1 blockade. More studies are warranted to establish the causality relationship between MSH4 and MSI.
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