ArticleCancer medicine2023
Mutational pattern off homologous recombination repair (HRR)-related genes in upper tract urothelial carcinoma.
Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 8 citations in OpenAlex.
- Predictive molecular alterations of prostate cancer brain metastases based on a companion diagnostic assay.Discover oncology · 2025Article
- IGF1R promotes radiation-induced HSCs activation by regulating DNA-PKcs-mediated DNA damage repair.Frontiers in cell and developmental biology · 2025Article
- The mutational pattern of homologous recombination repair genes in urothelial carcinoma and its correlation with immunotherapeutic response.Cancer medicine · 2023Article
- Review
- Mutational pattern off homologous recombination repair (HRR)-related genes in upper tract urothelial carcinoma.Cancer medicine · 2023Article
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7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHomologous recombination (HR) repair (HRR) has been indicated to be a biomarker for immunotherapy, chemotherapy, and poly-ADP ribose polymerase inhibitors inhibitors (PARPis). Nonetheless, their molecular correlates in upper tract urothelial carcinoma (UTUC) have not been well studied. This study aimed to explore the molecular mechanism and tumor immune profile of HRR genes and the relevance of their prognostic value in patients with UTUC. MATERIALS AND
methodsOne hundred and ninety-seven tumors and matched blood samples from Chinese UTUC were subjected to next-generation sequencing. A total of 186 patients from The Cancer Genome Atlas were included. Comprehensive analysis was performed.
resultsIn Chinese patients with UTUC, 5.01% harbored germline HRR gene mutations, and 1.01% had Lynch syndrome-related genes. A total of 37.6% (74/197) of patients carried somatic or germline HRR gene mutations. There was marked discrepancy in the mutation landscapes, genetic interactions, and driver genes between the HRR-mut cohorts and HRR-wt cohorts. Aristolochic acid signatures and defective DNA mismatch repair signatures only existed in individuals in the HRR-mut cohorts. Inversely, the unknown signature (signature A) and signature SBS55 only existed in patients in the HRR-wt cohorts. HRR gene mutations regulated immune activities by NKT cells, plasmacytoid dendritic cells, hematopoietic stem cell, and M1 macrophages. In patients with local recurrence, patients with HRR gene mutations had poorer DFS rates than patients with wild-type HRR genes.
conclusionsOur results imply that the detection of HRR gene mutations can predict recurrence in patients with UC. In addition, this study provides a path to explore the role of HRR-directed therapies, including PARPis, chemotherapy, and immunotherapy.
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