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

Munch-Petersen, Helga D.; Asmar, Fazila; Dimopoulos, Konstantinos; Areškevičiūtė, Aušrinė; Brown, Peter de Nully; Girkov, Mia Seremet; Pedersen, Anja; Sjö, Lene Dissing; Heegaard, Steffen; Broholm, Helle; Kristensen, Lasse Sommer; Ralfkiær, Elisabeth; Grønbæk, Kirsten

doi:10.1186/s40478-016-0307-6

Cited by 19 publications

(23 citation statements)

References 55 publications

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“…The dominantly negative effect exhibited in mutant TP53 can cause adverse therapeutic outcomes and early cancer recurrence [39]. Several studies included in our research also confirmed that TP53 mutations in the DBD are significantly correlated with poor OS in patients with NHLs [15,16,22]. In 2014, the American Association for Cancer Research (AACR) recommended two categories of precision medicine: Umbrella Trails and Basket Trails.…”

Section: Discussionsupporting

confidence: 76%

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TP53 mutation predicts the poor prognosis of non-Hodgkin lymphomas: Evidence from a meta-analysis

Liu

Ouyang

et al. 2017

PLoS ONE

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Non-Hodgkin lymphoma (NHL) is a group of malignant hematologic disorders with high heterogeneity. The diagnosis, clinical manifestations, classification, and prognosis of this condition differ among numerous NHL subgroups. The prognostic significance of the mutation of TP53, a tumor suppressor gene involved in cell cycle regulation, should be confirmed in NHL. In this study, our searching strategy and inclusion criteria were implemented, and the pooled hazard ratios (HRs) of the included studies were calculated directly or indirectly. A total of 1,851 patients were enrolled in 22 studies. A meta-analysis was then performed using STATA version 12.0 to confirm the correlation between the status of TP53 mutation and the survival time of patients with NHL. Statistical heterogeneity was assessed with a chi-square-based Q statistical test and Inconsistency index (I2) statistic. Sensitivity analysis and publication bias were also evaluated. A total of 22 studies were included in our meta-analysis. The pooled HR of the overall survival from 20 studies was 2.30 (95% CI: 1.92–2.76, p = 0.001) with heterogeneity (I2 30.2% p = 0.099). The pooled HR of the progression free survival provided in 5 articles was 2.28 (95% CI: 1.78–2.93, p = 0.001) with heterogeneity (I2 39.8% p = 0.156). No publication bias was found among the included studies, and sensitivity analysis suggested that the combined HRs were stable after any of the studies was excluded from our meta-analysis. This study identified the prognostic significance of TP53 mutation that varied in different NHL subgroups. The group with a mutated TP53 was significantly associated with poor prognosis in patients with NHL. This parameter is a valuable basis for accurate individual therapeutic regimens.

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Section: Discussionsupporting

confidence: 76%

“…Finally, 22 studies were identified in our meta-analysis [10,11,15–35]. The details of the 22 studies are listed in Table 1.…”

Section: Resultsmentioning

confidence: 99%

TP53 mutation predicts the poor prognosis of non-Hodgkin lymphomas: Evidence from a meta-analysis

Liu

Ouyang

et al. 2017

PLoS ONE

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“…82 TP53 mutations have been identified in 27-37% of cases. 83,84 Hypermethylation of DAPK1 or MGMT has been identified and may be therapeutic targets. 1,85…”

Section: Immunophenotypementioning

confidence: 99%

Diffuse large B-cell lymphoma variants: an update

et al. 2020

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“…Previous studies have suggested that genetic variants are associated with prognosis for patients suffering from metastatic colorectal cancer who are treated with oxaliplatin‐based chemotherapy . Several reports indicate that SNPs related to chemotherapy resistance exist in p53 signaling pathway genes . Most studies have shown that SNPs affect cancer prognosis by altering messenger RNA (mRNA) expression or by combining with microRNA .…”

Section: Discussionmentioning

confidence: 99%

“…22 Several reports indicate that SNPs related to chemotherapy resistance exist in p53 signaling pathway genes. [23][24][25] Most studies have shown that SNPs affect cancer prognosis by altering messenger RNA (mRNA) expression or by combining with microRNA. 26 However, the mechanisms whereby SNPs reportedly affect mRNA are inconsistent.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants in p53 signaling pathway genes predict chemotherapy efficacy in colorectal cancer

et al. 2019

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Background The murine double minute‐2 gene ( MDM2 ) was originally identified as predicting chemotherapy efficacy. However, little is known regarding the association between single nucleotide polymorphisms (SNPs) in the p53 signaling pathway and prognosis/chemotherapy sensitivity in colorectal cancer. Methods We analyzed the association between 111 SNPs in 22 p53 signaling pathway genes and both progression‐free survival (PFS) and disease control rate (DCR) using Cox regression and logistics regression analysis. The false discovery rate method was used for correction of multiple testing. Secondary structure was predicted by RNAfold. Expression qualitative trait locus analysis and mRNA expression differences were assessed using the GTEx and TCGA databases. Results We found that the rs747828 C allele of TP73 was significantly associated with reduced PFS (HR = 1.64, 95% CI = 1.27‐2.12, P = 2.00 × 10 −4 ) in the additive model. In the stratified analysis, the rs747828 C allele was significantly associated with both reduced PFS ( P = 1.40 × 10 −3 ) and DCR ( P = 1.82 × 10 −2 ) in oxaliplatin‐based chemotherapy. The secondary structure of TP73 was altered in response to different rs747828 genotypes. Although the rs747828 C allele was not associated with messenger RNA (mRNA) TP73 expression, it was significantly associated with increased mRNA TP73‐AS1 expression levels in sigmoid tissues. TP73 mRNA was significantly overexpressed in tumor tissues compared to adjacent normal tissues ( P = 2.36 × 10 −19 ). Conclusion Our findings indicate that functional genetic variants of TP73 mediate the response to chemotherapy in colorectal cancer.

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

Cited by 19 publications

References 55 publications

TP53 mutation predicts the poor prognosis of non-Hodgkin lymphomas: Evidence from a meta-analysis

TP53 mutation predicts the poor prognosis of non-Hodgkin lymphomas: Evidence from a meta-analysis

Diffuse large B-cell lymphoma variants: an update

Genetic variants in p53 signaling pathway genes predict chemotherapy efficacy in colorectal cancer

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