Martinez-Delgado B, Richart A, García M J, Robledo M, Osorio A, Cebrian A, Rivas C, Benitez J
Departments of Genetics, Haematology and Pathology, Fundación Jimenez Díaz, Av. Reyes Católicos 2, 28040 Madrid, Spain.
Br J Haematol. 2000 Apr;109(1):97-103. doi: 10.1046/j.1365-2141.2000.01991.x.
The hypermethylation of p16ink4a and p15ink4b genes have been described as an inactivating mechanism alternative to deletions and mutations that accounts for a relatively high proportion of cancers, including non-Hodgkin's lymphomas (NHLs). To investigate whether detection of abnormal methylation could have clinical applications in the management and follow-up of lymphomas, we have analysed the behaviour and evolution of p16ink4a and p15ink4b methylation in 13 NHL cases undergoing chemotherapy. All cases were also analysed for the presence of monoclonal rearrangements of immunoglobulin or T-cell receptor genes. Six patients showed methylation in at least one of these genes at diagnosis, whereas in two other cases methylation appeared during the treatment. The other five cases were always unmethylated. Methylation was detected when any histological or molecular evidence of disease was present, suggesting a good correlation between methylation and disease. In some cases, we were able to detect methylation in patients at complete remission and without evidence of monoclonal cell population, indicating a high sensitivity of the PCR to detect methylation. These results suggest that p16ink4a and p15ink4b methylation could be good markers of disease and could be helpful in identifying lymphoma patients at risk of relapse.
p16ink4a和p15ink4b基因的高甲基化已被描述为一种除缺失和突变之外的失活机制，其在包括非霍奇金淋巴瘤（NHL）在内的相对高比例癌症中发挥作用。为了研究异常甲基化检测在淋巴瘤的管理和随访中是否具有临床应用价值，我们分析了13例接受化疗的NHL患者中p16ink4a和p15ink4b甲基化的行为和演变。所有病例还分析了免疫球蛋白或T细胞受体基因的单克隆重排情况。6例患者在诊断时至少其中一个基因出现甲基化，而另外2例在治疗期间出现甲基化。其他5例始终未甲基化。当存在任何疾病的组织学或分子证据时均可检测到甲基化，这表明甲基化与疾病之间具有良好的相关性。在某些情况下，我们能够在完全缓解且无单克隆细胞群证据的患者中检测到甲基化，这表明PCR检测甲基化具有高灵敏度。这些结果表明，p16ink4a和p15ink4b甲基化可能是疾病的良好标志物，有助于识别有复发风险的淋巴瘤患者。
