Tumor suppressor p16 methylation in multiple myeloma:: biological and clinical implications
Tumor suppressor p16 methylation in multiple myeloma:: biological and clinical implications
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DOI：
10.1182/blood-2006-05-024661
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发表时间：
2007-02-01
期刊：
影响因子：
20.3
通讯作者：
Fonseca, Rafael
中科院分区：
文献类型：
--
作者：
Gonzalez-Paz, Natalia;Chng, Wee J.;Fonseca, Rafael
尽管已有研究，但p16基因甲基化在多发性骨髓瘤（MM）中的生物学和临床意义仍不清楚。在这项综合研究中，使用甲基化特异性PCR (MS-PCR)，我们发现p16甲基化是相对常见的，发生在未确定意义的单克隆γ病（MGUS, n = 17），阴烧多发性骨髓瘤（SMM, n = 40）和MM （n = 522）中，患病率分别为24%，28%和34%。然而，p16甲基化似乎不影响基因表达水平。在一项有长期随访信息的患者大队列研究中（n = 439）， p16甲基化与非p16甲基化患者的总生存率无差异。我们还发现p16甲基化与主要细胞遗传学类别之间没有关联，尽管它在17p13.1缺失（p53位点）的患者中更为常见，这是MM的遗传进展事件。此外，p16甲基化对周期没有明显影响，因为p16甲基化患者和非p16甲基化患者之间的浆细胞标记指数（增殖的直接测量）也没有差异。我们的研究结果质疑p16甲基化在PC肿瘤发生中的主要作用，我们现在认为p16甲基化可能是与疾病进展相关的整体表观遗传变化的标志，没有明显的直接生物学或临床后果。
The biological and clinical implications of p16 gene methylation in multiple myeloma (MM) are still unclear despite previous studies. In this comprehensive study, using methylation-specific PCR (MS-PCR), we show that p16 methylation is relatively common and occurs in monoclonal gammopathy of undetermined significance (MGUS; n = 17), smoldering multiple myeloma (SMM; n = 40), and MM (n = 522) at a prevalence of 24%, 28%, and 34%, respectively. However, p 16 methylation does not appear to affect gene expression level. In a large cohort of patients with long-term follow-up information (n = 439), there was no difference in overall survival between patients with or without p16 methylation. We also found no association between p16 methylation and the main cytogenetic categories, although it was more common among patients with 17p13.1 deletions (p53 locus), a genetic progression event in MM. In addition, p16 methylation has no apparent effect on the cycle because there was also no difference in the plasma cell labeling index (a direct measurement of proliferation) between patients with and without p16 methylation. Our results question a major role for p16 methylation in the oncogenesis of the PC neoplasm, and we now believe p16 methylation may be a marker for overall epigenetic changes associated with disease progression, with no obvious direct biological or clinical consequences.