Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma

Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Improvements in overall survival have been observed with the introduction of rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), however, prognostic markers ar...

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Main Authors: Kristensen, Lasse Sommer, Asmar, Fazila, Dimopoulos, Konstantinos, Nygaard, Mette Kathrine, Aslan, Derya, Hansen, Jakob Werner, Ralfkiaer, Elisabeth, Grønbæk, Kirsten
Format: Online
Language:English
Published: Impact Journals LLC 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259438/
id pubmed-4259438
recordtype oai_dc
spelling pubmed-42594382014-12-10 Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma Kristensen, Lasse Sommer Asmar, Fazila Dimopoulos, Konstantinos Nygaard, Mette Kathrine Aslan, Derya Hansen, Jakob Werner Ralfkiaer, Elisabeth Grønbæk, Kirsten Research Paper Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Improvements in overall survival have been observed with the introduction of rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), however, prognostic markers are still needed. Methylation of the death associated protein kinase (DAPK or DAPK1) gene and TP53 mutations are likely to have prognostic value in DLBCL. We have assessed TP53 mutations and allelic DAPK1 methylation patterns in a cohort of 119 DLBCL patients uniformly treated with R-CHOP-like regimens. We found that DAPK1 promoter methylation was associated with shorter overall survival (p=0.017) and disease-specific survival (p=0.023). In multivariate analyses DAPK1 methylation remained as an independent prognostic factor predicting disease-specific survival (p=0.038). When only considering individuals heterozygous for the rs13300553 SNP monoallelic methylation of the A-allele was associated with shorter overall- and disease-specific survival (p<0.001). Patients carrying both DAPK1 methylation and a TP53 mutation had an inferior survival compared to patients carrying only one of these molecular alterations, however, this was borderline statistically significant. Allele-specific DAPK1 methylation patterns were also studied in a cohort of 67 multiple myeloma patients, and all of the methylated multiple myeloma samples heterozygous for the rs13300553 SNP were methylated on both alleles. Impact Journals LLC 2014-11-03 /pmc/articles/PMC4259438/ /pubmed/25229255 Text en Copyright: © 2014 Kristensen et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Kristensen, Lasse Sommer
Asmar, Fazila
Dimopoulos, Konstantinos
Nygaard, Mette Kathrine
Aslan, Derya
Hansen, Jakob Werner
Ralfkiaer, Elisabeth
Grønbæk, Kirsten
spellingShingle Kristensen, Lasse Sommer
Asmar, Fazila
Dimopoulos, Konstantinos
Nygaard, Mette Kathrine
Aslan, Derya
Hansen, Jakob Werner
Ralfkiaer, Elisabeth
Grønbæk, Kirsten
Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma
author_facet Kristensen, Lasse Sommer
Asmar, Fazila
Dimopoulos, Konstantinos
Nygaard, Mette Kathrine
Aslan, Derya
Hansen, Jakob Werner
Ralfkiaer, Elisabeth
Grønbæk, Kirsten
author_sort Kristensen, Lasse Sommer
title Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma
title_short Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma
title_full Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma
title_fullStr Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma
title_full_unstemmed Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma
title_sort hypermethylation of dapk1 is an independent prognostic factor predicting survival in diffuse large b-cell lymphoma
description Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Improvements in overall survival have been observed with the introduction of rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), however, prognostic markers are still needed. Methylation of the death associated protein kinase (DAPK or DAPK1) gene and TP53 mutations are likely to have prognostic value in DLBCL. We have assessed TP53 mutations and allelic DAPK1 methylation patterns in a cohort of 119 DLBCL patients uniformly treated with R-CHOP-like regimens. We found that DAPK1 promoter methylation was associated with shorter overall survival (p=0.017) and disease-specific survival (p=0.023). In multivariate analyses DAPK1 methylation remained as an independent prognostic factor predicting disease-specific survival (p=0.038). When only considering individuals heterozygous for the rs13300553 SNP monoallelic methylation of the A-allele was associated with shorter overall- and disease-specific survival (p<0.001). Patients carrying both DAPK1 methylation and a TP53 mutation had an inferior survival compared to patients carrying only one of these molecular alterations, however, this was borderline statistically significant. Allele-specific DAPK1 methylation patterns were also studied in a cohort of 67 multiple myeloma patients, and all of the methylated multiple myeloma samples heterozygous for the rs13300553 SNP were methylated on both alleles.
publisher Impact Journals LLC
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259438/
_version_ 1613165233091641344

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