Advanced Rai Stage in Patients with Chronic Lymphocytic Leukaemia Correlates with Simultaneous Hypermethylation of Plural Tumour Suppressor Genes

Abstract

Hypermethylation of CpG islands within gene promoters is one of various mechanisms of gene silencing involved in the pathogenesis of human cancer. By using methylation-specific polymerase chain reaction we explored aberrant promoter methylation of five tumour suppressor genes in 29 patients with chronic lymphocytic leukaemia.

Aberrant methylation of DLC1, SHP1, p15 and p16 occurred, respectively, in 89.7 %, 70 %, 62.1 % and 31 % of patients at diagnosis. Lamin A/C was unmethylated in all the samples.

Hypermethylation of at least one gene was detected in 96.6 % of patients. Concurrent methylation of two or more genes correlated with Rai stage at diagnosis.

Keywords

• chronic lymphocytic leukaemia
• aberrant hypermethylation
• tumour suppressor genes
• Rai stage
• methylation-specific polymerase chain reaction
• ABERRANT PROMOTER HYPERMETHYLATION
• VARIABLE-REGION MUTATIONS
• CPG ISLAND METHYLATION
• COMMON HUMAN CANCERS
• B-CELL LYMPHOMAS
• DNA METHYLATION
• CD38 EXPRESSION
• HEPATOCELLULAR-CARCINOMA
• GENOMIC ABERRATIONS
• LAMIN A/C