Untersuchungen über Veränderungen des Epigenoms bei der chronischen lymphatischen Leukämie

Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. Apart from chromosomal alterations comprising deletions and numeric aberrations there is increasing evidence that epigenetic processes contribute to the malignant phenotype of CLL. There is no known pathogenic mechanism inducing CLL, in fact concomitant alterations in various signaling pathways seem to lead to dysregulation of cell cycle and apoptosis. A large number of genes affecting cancer-related pathways may be dysregulated by epigenetic silencing in virtually all tumor types. Using a candidate-gene approach we analyzed by methylation-specific polymerase chain reaction the CpG island methylation status of 17 well-characterized cancer-related genes in 32 patients with CLL. Aberrant methylation among the samples of patients with CLL was shown for SFRP1 (68.8%), SFRP2 (65.6%), DAPK1 (50.0%), E cadherin (21.9%), SFRP4 (15.6%), SOCS3 (15.6%), p15 (9.4%), p16 (6.3%), RARbeta2 (3.1%), SFRP5 (3.1%) und TIMP3 (3.1%). For DAPK2, hMLH1, MGMT, p73, SOCS1 and TIMP2 no hypermethylation was detected. Hypermethylation of at least one gene was observed in 90.6% of the samples. Up to 7 of 17 gene promoter regions examined were concurrently methylated. Hypermethylation occurred in all Rai stages without a preference for advanced stages. Our results show that aberrant CpG island methylation affecting cancer-related pathways such as Wnt signaling, regulation of apoptosis, cell cycle control and tissue invasion is a common phenomenon in CLL. Epigenetic silencing of tumor suppressor genes as well as other critical genes is an alternative mechanism of gene inactivation by mutations or deletions in malignant cells. In addition to genetic alterations, epigenetic disturbances may be involved in the pathogenesis of CLL and thus may provide a molecular rationale for therapeutic approaches.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2009

Author dc:creator

• Seeliger, Barbara

Contributors dc:contributor

• Galm, Oliver

• info:eu-repo/classification/ddc/610
• Epigenetik
• Apoptosis
• Zellzyklus
• Medizin
• Apoptose
• Chronische lymphatische Leukämie
• DNA-Methylierung
• Wnt-Signalweg
• MSP
• chronic lymphocytic leukemia
• DNA methylation
• epigenetics
• Wnt-pathway

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113540%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A51228