Methylation Analysis of Cell Cycle Control Genes in Adult T-Cell Leukemia/Lymphoma

Abstract

Central to many cancers is the aberrant expression of genes that regulate the cell cycle including the cyclin-dependent kinase inhibitors known as p15^INK4b and p16^INK4a, p14^ARF and the retinoblastoma (RB) protein. We performed a detailed analysis of the methylation status of these genes by methylation specific polymerase chain reaction (MSP) in tumor cells of 35 adult T-cell leukemia/lymphoma (ATL) patients. We found in nine of 35 cases (26%) at least one gene methylated. The frequency of p15^INK4b methylation was 7 of 35 (20%). The incidence of methylation of p14^ARF and p16^INKa was two of 35 (6%) and one of 35 (3%), respectively. The RB gene was not found to be methylated in any of the ATL samples. The data indicate that inactivation of these cell cycle regulatory genes by hypermethylation is important in the development of ATL.

Key Words:

• adult T-cell leukemia/lymphoma
• retinoblastoma protein
• cell cycle control genes
• methylation
• methylation specific polymerase chain reaction