Methylation analysis of cell cycle control genes in adult T-cell leukemia/lymphoma.

Central to many cancers is the aberrant expression of genes that regulate the cell cycle including the cyclin-dependent kinase inhibitors known as p15INK4b and p16INK4a, p14ARF 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 p15INK4b methylation was 7 of 35 (20%). The incidence of methylation of p14ARF and p16INK4a 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.