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Mendeley readers
Attention Score in Context
| Title |
TP53 hotspot mutations are predictive of survival in primary central nervous system lymphoma patients treated with combination chemotherapy
|
|---|---|
| Published in |
Acta Neuropathologica Communications, April 2016
|
| DOI | 10.1186/s40478-016-0307-6 |
| Pubmed ID | |
| Authors |
Helga D. Munch-Petersen, Fazila Asmar, Konstantinos Dimopoulos, Aušrinė Areškevičiūtė, Peter Brown, Mia Seremet Girkov, Anja Pedersen, Lene D. Sjö, Steffen Heegaard, Helle Broholm, Lasse S. Kristensen, Elisabeth Ralfkiaer, Kirsten Grønbæk |
| 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. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 2% |
| Denmark | 1 | 2% |
| Unknown | 47 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 8 | 16% |
| Researcher | 8 | 16% |
| Other | 6 | 12% |
| Student > Bachelor | 4 | 8% |
| Student > Master | 4 | 8% |
| Other | 10 | 20% |
| Unknown | 9 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 19 | 39% |
| Biochemistry, Genetics and Molecular Biology | 6 | 12% |
| Nursing and Health Professions | 3 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 2% |
| Environmental Science | 1 | 2% |
| Other | 4 | 8% |
| Unknown | 15 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 April 2016.
All research outputs
#17,799,386
of 22,865,319 outputs
Outputs from Acta Neuropathologica Communications
#1,199
of 1,378 outputs
Outputs of similar age
#205,119
of 298,997 outputs
Outputs of similar age from Acta Neuropathologica Communications
#27
of 31 outputs
Altmetric has tracked 22,865,319 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,378 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.8. This one is in the 10th percentile – i.e., 10% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 298,997 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 31 others from the same source and published within six weeks on either side of this one. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.