Genome-wide array-based methylation profiling reveals preferential methylation of homeobox transcription factor genes in mantle cell lymphoma and pro-apoptotic genes in chronic lymphocytic leukemia
(English)Manuscript (preprint) (Other academic)
Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) are B-cell malignancies that differ with regards to biological and clinical characteristics. Aberrant DNA methylation has been described for each disorder, but comparison between the two entities is lacking. We employed high-resolution methylation microarrays (27,578 CpG sites) to compare methylation profiles in 20 MCL (10 each with high/low proliferation signature) and 30 CLL (15 IGHV mutated, stereotyped subset #4 and 15 IGHV unmutated, stereotyped subset #1) samples. Distinct differences in methylation patterns were revealed between MCL and CLL, where MCL displayed a more homogenous profile. When comparing MCL and CLL/subsets, 51 genes were consistently identified as differentially methylated in all comparisons. Among 19 genes methylated in MCL, six were homeobox transcription factors (e.g. HLXB9, HOXA13), whereas unmethylated loci in MCL included genes enhancing proliferation and tumor progression (e.g. MERTK and CAMP). In contrast, apoptosis-related genes were prominent among genes methylated in CLL (e.g. DYRK2 and CYFIP2). Correlation between promoter methylation and gene expression was confirmed for selected genes using RQ-PCR. Notably, homeobox genes were not expressed in either entity, implying different gene silencing mechanisms in MCL and CLL. In summary, the differences in global methylation profiles between MCL and CLL have unfolded distinct epigenetic mechanisms operating in each disease.
mantle cell lymphoma, chronic lymphocytic leukemia, Genome-wide array-based methylation profiling
IdentifiersURN: urn:nbn:se:uu:diva-132886OAI: oai:DiVA.org:uu-132886DiVA: diva2:359577