Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden.
Leuk Res. 2011 Apr;35(4):438-43. doi: 10.1016/j.leukres.2010.10.001. Epub 2010 Oct 29.
The p16(INK4a) tumor suppressor gene can be inactivated by a variety of events including promoter hypermethylation. In diffuse large B-cell lymphoma (DLBCL), p16(INK4a) methylation has been associated with advanced disease stage and higher IPI. The prognostic impact of p16(INK4a) methylation in DLBCL remains unclear; however, it has been suggested to correlate with inferior outcome. To further investigate the clinical impact of p16(INK4a) methylation in DLBCL, promoter methylation of this gene was assessed quantitatively by pyrosequencing. Forty-two of 113 (37%) DLBCL patients with methylation level above 5% were categorized as methylated and subsequently divided into low, intermediate and high methylation categories. Overall, no association was shown between the extent of p16(INK4a) methylation and patients' clinical characteristics, except disease stage (P=0.049). Moreover, we could not reveal any impact of p16(INK4a) methylation on lymphoma-specific survival. Although >25% of p16(INK4a) methylation correlated with a better progression-free survival (P=0.048) in patients <65 years old, the significance of this finding, if any, needs to be further investigated. In conclusion, our finding questions the role of p16(INK4a) promoter methylation as a negative prognostic factor in DLBCL.
p16（INK4a）肿瘤抑制基因可因多种事件失活，包括启动子超甲基化。在弥漫性大 B 细胞淋巴瘤（DLBCL）中，p16（INK4a）甲基化与晚期疾病阶段和更高的 IPI 相关。p16（INK4a）甲基化在 DLBCL 中的预后影响尚不清楚；然而，据报道它与不良预后相关。为了进一步研究 p16（INK4a）在 DLBCL 中的甲基化的临床影响，通过焦磷酸测序定量评估了该基因的启动子甲基化。在 113 例 DLBCL 患者中，有 42 例（37%）甲基化水平高于 5%，被归类为甲基化，并随后分为低、中和高甲基化类别。总体而言，p16（INK4a）甲基化的程度与患者的临床特征之间没有关联，除了疾病阶段（P=0.049）。此外，我们无法揭示 p16（INK4a）甲基化对淋巴瘤特异性生存的任何影响。尽管 >25%的 p16（INK4a）甲基化与<65 岁患者的无进展生存（P=0.048）相关，但如果存在任何意义，需要进一步研究。总之，我们的发现对 p16（INK4a）启动子甲基化作为 DLBCL 中负预后因素的作用提出了质疑。
