ArticleActa neuropathologica communications2016
TP53 hotspot mutations are predictive of survival in primary central nervous system lymphoma patients treated with combination chemotherapy.
Article in Acta neuropathologica communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- Pooled it
- TP53 mutation predicts the poor prognosis of non-Hodgkin lymphomas: Evidence from a meta-analysis.PloS one · 2017Pooled it
- Review
- CAR-T cell therapy in TP53-mutated CNS lymphoma: overcoming a high-risk genetic barrier.Frontiers in medicine · 2025Article
- The Impact of Mutational Hotspots on Cancer Survival.Cancers · 2024Article
- Clinicopathological analysis and specific discriminating markers of interleukin detection in cerebrospinal fluid with primary central nervous system lymphoma: results from a retrospective study.Annals of hematology · 2023Article
- The Methylation of the p53 Targets the GenesGenes · 2022Article
- A genetically distinct pediatric subtype of primary CNS large B-cell lymphoma is associated with favorable clinical outcome.Blood advances · 2022Article
- Review
- Case Report: Identification of Potential Prognosis-RelatedFrontiers in endocrinology · 2021Article
- Genetic variants in p53 signaling pathway genes predict chemotherapy efficacy in colorectal cancer.Cancer medicine · 2019Article
- Rare cases of primary central nervous system anaplastic variant of diffuse large B-cell lymphoma.Diagnostic pathology · 2019Article
- Primary central nervous system lymphoma: essential points in diagnosis and management.Medical oncology (Northwood, London, England) · 2017Review
- Mutation Frequencies in Endometrial Cancer Patients of Different Ethnicities and Tumor Grades: An Analytical Study.Saudi journal of medicine & medical sciencesArticle
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary central nervous system lymphoma (PCNSL) is an aggressive variant of diffuse large B-cell lymphoma (DLBCL) confined to the CNS. TP53 mutations (MUT-TP53) were investigated in the context of MIR34A/B/C- and DAPK promoter methylation status, and associated with clinical outcomes in PCNSL patients. In a total of 107 PCNSL patients clinical data were recorded, histopathology reassessed, and genetic and epigenetic aberrations of the p53-miR34-DAPK network studied. TP53 mutational status (exon 5-8), with structural classification of single nucleotide variations according to the IARC-TP53-Database, methylation status of MIR34A/B/C and DAPK, and p53-protein expression were assessed. The 57/107 (53.2 %) patients that were treated with combination chemotherapy +/- rituximab (CCT-treated) had a significantly better median overall survival (OS) (31.3 months) than patients treated with other regimens (high-dose methotrexate/whole brain radiation therapy, 6.0 months, or no therapy, 0.83 months), P < 0.0001. TP53 mutations were identified in 32/86 (37.2 %), among which 12 patients had hotspot/direct DNA contact mutations. CCT-treated patients with PCNSL harboring a hotspot/direct DNA contact MUT-TP53 (n = 9) had a significantly worse OS and progression free survival (PFS) compared to patients with non-hotspot/non-direct DNA contact MUT-TP53 or wild-type TP53 (median PFS 4.6 versus 18.2 or 45.7 months), P = 0.041 and P = 0.00076, respectively. Multivariate Cox regression analysis confirmed that hotspot/direct DNA contact MUT-TP53 was predictive of poor outcome in CCT-treated PCNSL patients, P = 0.012 and P = 0.008; HR: 1.86 and 1.95, for OS and PFS, respectively. MIR34A, MIR34B/C, and DAPK promoter methylation were detected in 53/93 (57.0 %), 80/84 (95.2 %), and 70/75 (93.3 %) of the PCNSL patients with no influence on survival. Combined MUT-TP53 and MIR34A methylation was associated with poor PFS (median 6.4 versus 38.0 months), P = 0.0070. This study suggests that disruption of the p53-pathway by MUT-TP53in hotspot/direct DNA contact codons is predictive of outcome in CCT-treated PCNSL patients, and concomitant MUT-TP53 and MIR34A methylation are associated with poor PFS.
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