Publicações científicas

A comprehensive microarray-based DNA methylation study of 367 hematological neoplasms

Martin-Subero JI, Ammerpohl O, Bibikova M, Wickham-Garcia E, Agirre X, Alvarez S, Brüggemann M, Bug S, Calasanz MJ, Deckert M, Dreyling M, Du MQ, Dürig J, Dyer MJ, Fan JB, Gesk S, Hansmann ML, Harder L, Hartmann S, Klapper W, Küppers R, Montesinos-Rongen M, Nagel I, Pott C, Richter J, Román-Gómez J, Seifert M, Stein H, Suela J, Trümper L, Vater I, Prosper F, Haferlach C, Cruz Cigudosa J, Siebert R.
Institute of Human Genetics, Christian-Albrechts University, Kiel, Germany.

Revisão:PloS One

Data: 11/Set/2009

Área de Terapia Celular [ES]

BACKGROUND
Alterations in the DNA methylation pattern are a hallmark of leukemias and lymphomas. However, most epigenetic studies in hematologic neoplasms (HNs) have focused either on the analysis of few candidate genes or many genes and few HN entities, and comprehensive studies are required.

METHODOLOGY/PRINCIPAL FINDINGS
Here, we report for the first time a microarray-based DNA methylation study of 767 genes in 367 HNs diagnosed with 16 of the most representative B-cell (n = 203), T-cell (n = 30), and myeloid (n = 134) neoplasias, as well as 37 samples from different cell types of the hematopoietic system. Using appropriate controls of B-, T-, or myeloid cellular origin, we identified a total of 220 genes hypermethylated in at least one HN entity. In general, promoter hypermethylation was more frequent in lymphoid malignancies than in myeloid malignancies, being germinal center mature B-cell lymphomas as well as B and T precursor lymphoid neoplasias those entities with highest frequency of gene-associated DNA hypermethylation.

We also observed a significant correlation between the number of hypermethylated and hypomethylated genes in several mature B-cell neoplasias, but not in precursor B- and T-cell leukemias. Most of the genes becoming hypermethylated contained promoters with high CpG content, and a significant fraction of them are targets of the polycomb repressor complex. Interestingly, T-cell prolymphocytic leukemias show low levels of DNA hypermethylation and a comparatively large number of hypomethylated genes, many of them showing an increased gene expression.

CONCLUSIONS/SIGNIFICANCE
We have characterized the DNA methylation profile of a wide range of different HNs entities. As well as identifying genes showing aberrant DNA methylation in certain HN subtypes, we also detected six genes--DBC1, DIO3, FZD9, HS3ST2, MOS, and MYOD1--that were significantly hypermethylated in B-cell, T-cell, and myeloid malignancies. These might therefore play an important role in the development of different HNs.

CITAÇÃO DO ARTIGO  PLoS One. 2009 Sep 11;4(9):e6986

talvezlhe interesse

QUE TECNOLOGIA UTILIZAMOS? 

A Clínica é o hospital privado com maiores recursos tecnológicos de Espanha, tudo num único centro.

Imagen de un PET, tecnología de vanguardia en la Clínica Universidad de Navarra

OS NOSSOS
PROFISSIONAIS

Os profissionais da Clínica realizam um trabalho contínuo de investigação e formação, sempre em benefício do paciente.

Imagen profesionales de la Clínica Universidad de Navarra

RAZÕES PARA VIR
À CLÍNICA

Conheça porque é que somos diferentes em relação a outros centros sanitários. Qualidade, rapidez, comodidade e resultados.

Imagen del edificio de la Clínica Universidad de Navarra