TP53 hotspot mutations are predictive of survival in primary central nervous system lymphoma patients treated with combination chemotherapy

• Published in: Acta neuropathologica communications 2016-04, Vol.4 (38), p.40-40, Article 40
• Main Authors: Munch-Petersen, Helga D, Asmar, Fazila, Dimopoulos, Konstantinos, Areškevičiūtė, Aušrinė, Brown, Peter, Girkov, Mia Seremet, Pedersen, Anja, Sjö, Lene D, Heegaard, Steffen, Broholm, Helle, Kristensen, Lasse S, Ralfkiaer, Elisabeth, Grønbæk, Kirsten
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Antigens, CD - metabolism; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer; Care and treatment; Central Nervous System Neoplasms - drug therapy; Central Nervous System Neoplasms - genetics; Central Nervous System Neoplasms - mortality; Chemotherapy; Death-Associated Protein Kinases - genetics; Death-Associated Protein Kinases - metabolism; Denmark; Development and progression; DNA Methylation - genetics; DNA Mutational Analysis; Female; Gene mutations; Genetic aspects; Health aspects; Humans; Lymphoma - drug therapy; Lymphoma - genetics; Lymphoma - mortality; Lymphomas; Male; MicroRNAs - genetics; MicroRNAs - metabolism; Mutation - genetics; Nervous system cancer; Patient outcomes; Pharmacogenetics; Predictive Value of Tests; Properties; Retrospective Studies; Survival Analysis; Treatment Outcome; Tumor proteins; Tumor Suppressor Protein p53 - genetics
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-016-0307-6

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