Inactivation Pattern of p16 Gene in Non-Hodgkin's Lymphomas

Abstract

BACKGROUND Loss of heterozygosity (LOH) and mutation of the p16 tumor suppressor gene have been detected in non-Hodgkin's lymphomas (NHLs). Recently, hypermethylation of the p16 gene has been reported. The role of p16 gene alterations in the genesis of NHLs and their high-grade transformations require explanation. METHODS LOH of D9S171 and IFNA microsatellite markers, DNA hypermethylation, and mutation of exon 1 and 2A were assessed in 43 cases of NHLs. The genetic abnormalities were compared with the protein expression by immunohistochemistry, and they were evaluated according to the histologic subtypes, grades and immunophenotypes. RESULTS DNA hypermethylation was the most common p16 gene abnormality and was found in 30 of 39 cases (76.9%). Eight cases (18.6%) showed LOH in one or both microsatellite markers, and five cases (11.6%) showed mutations in exon 1 or 2A. Loss of protein expression was seen in 17 cases (39.5%) and was associated with mutation and LOH. Loss of protein was more frequent in high-grade lymphomas than in low-grade lymphomas. CONCLUSION These results suggest that the functional loss of the p16 gene contributes to the development of NHLs, especially to the development of high-grade lymphomas.