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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.
Afiliación
  • Kristensen LS; Department of Haematology, Rigshospitalet, Blegdamsvej 9, 2100-DK, Copenhagen, Denmark.
  • Asmar F; Department of Haematology, Rigshospitalet, Blegdamsvej 9, 2100-DK, Copenhagen, Denmark.
  • Dimopoulos K; Department of Haematology, Rigshospitalet, Blegdamsvej 9, 2100-DK, Copenhagen, Denmark.
  • Nygaard MK; Department of Haematology, Aalborg University Hospital, Mølleparkvej 4, 9000-DK, Aalborg, Denmark.
  • Aslan D; Department of Haematology, Rigshospitalet, Blegdamsvej 9, 2100-DK, Copenhagen, Denmark.
  • Hansen JW; Department of Haematology, Rigshospitalet, Blegdamsvej 9, 2100-DK, Copenhagen, Denmark.
  • Ralfkiaer E; Department of Pathology, Rigshospitalet, Copenhagen, Denmark.
  • Grønbæk K; Department of Haematology, Rigshospitalet, Blegdamsvej 9, 2100-DK, Copenhagen, Denmark.
Oncotarget ; 5(20): 9798-810, 2014 Oct 30.
Article en En | MEDLINE | ID: mdl-25229255
ABSTRACT
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.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfoma de Células B Grandes Difuso / Metilación de ADN / Proteínas Quinasas Asociadas a Muerte Celular Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Oncotarget Año: 2014 Tipo del documento: Article País de afiliación: Dinamarca

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfoma de Células B Grandes Difuso / Metilación de ADN / Proteínas Quinasas Asociadas a Muerte Celular Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Oncotarget Año: 2014 Tipo del documento: Article País de afiliación: Dinamarca