DNA 甲基化分析可对艾滋病相关淋巴瘤进行分类。

DNA methylation profiling can classify HIV-associated lymphomas.

机构信息

aDepartment of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, Shinjuku bDepartment of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Honkomagome, Bunkyo cBiostatistics Section, Department of Clinical Research and Informatics, Clinical Research Center, National Center for Global Health and Medicine, Shinjuku dDepartment of Human Genetic, School of Medicine, The University of Tokyo, Bunkyo, Tokyo eGraduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba fDepartment of Pathology gAIDS Clinical Center hDivision of Hematology, Internal Medicine, National Center for Global Health and Medicine Hospital, Shinjuku iDepartment of Pathology, School of Medicine, Kyorin University, Mitaka, Tokyo, Japan.

出版信息

AIDS. 2014 Feb 20;28(4):503-10. doi: 10.1097/QAD.0000000000000120.

DOI:10.1097/QAD.0000000000000120

PMID:24335480

Abstract

BACKGROUND

HIV-positive patients have a 60-fold to 200-fold increased incidence of non-Hodgkin lymphomas, including Burkitt lymphoma, diffuse large B-cell lymphoma, and primary central nervous system lymphoma. HIV-associated lymphomas frequently have features such as extranodal involvement, decreased responses to standard chemotherapy, and high relapse rates, which indicate a poor prognosis. General pathological features do not clearly differentiate HIV-associated lymphomas from non-HIV lymphomas.

METHODS

To investigate the features of HIV-associated lymphomas, we performed genome-wide DNA methylation profiling of HIV and non-HIV lymphomas using Illumina GoldenGate Methylation Cancer Panel I and Illumina Infinium HumanMethylation450 BeadChip microarrays. DNA methylation profiles in HIV-associated and non-HIV lymphomas were characterized using unsupervised hierarchical clustering analyses.

RESULTS

The analyses of promoter regions revealed unique DNA methylation profiles in HIV-associated lymphomas, suggesting profile differences compared with non-HIV lymphomas, which implies specific gene regulation in HIV-associated lymphoma involving DNA methylation. Based on HumanMethylation450 BeadChip data, 2541 target sites were selected as differing significantly in comparisons between HIV-associated and non-HIV-associated lymphomas using Wilcoxon's rank-sum test (P <0.05) and Δβ values more than 0.30. Recurrent cases of HIV-associated lymphoma had different profiles compared with nonrecurrent HIV lymphomas.

CONCLUSION

DNA methylation profiling indicated that 2541 target sites differed significantly in HIV-associated lymphoma, which may partly explain the poor prognosis. Our data indicate that the methylation profiles of target genes have potential in elucidating HIV-associated lymphomagenesis and can serve as new prognostic markers.

摘要

背景

HIV 阳性患者非霍奇金淋巴瘤的发病率增加了 60 到 200 倍，包括伯基特淋巴瘤、弥漫性大 B 细胞淋巴瘤和原发性中枢神经系统淋巴瘤。HIV 相关淋巴瘤常具有结外侵犯、对标准化疗反应降低和高复发率等特征，提示预后不良。一般病理特征不能明确区分 HIV 相关淋巴瘤和非 HIV 淋巴瘤。

方法

为了研究 HIV 相关淋巴瘤的特征，我们使用 Illumina GoldenGate Methylation Cancer Panel I 和 Illumina Infinium HumanMethylation450 BeadChip 微阵列对 HIV 和非 HIV 淋巴瘤进行了全基因组 DNA 甲基化谱分析。采用无监督层次聚类分析对 HIV 相关和非 HIV 相关淋巴瘤的 DNA 甲基化谱进行了描述。

结果

启动子区域分析显示 HIV 相关淋巴瘤存在独特的 DNA 甲基化谱，提示与非 HIV 淋巴瘤存在谱差异，这意味着 HIV 相关淋巴瘤中存在特定的基因调控涉及 DNA 甲基化。基于 HumanMethylation450 BeadChip 数据，采用 Wilcoxon 秩和检验（P ＜0.05）和Δβ值大于 0.30，在 HIV 相关和非 HIV 相关淋巴瘤之间比较，选择了 2541 个差异显著的靶位。与非复发性 HIV 淋巴瘤相比，复发性 HIV 相关淋巴瘤具有不同的谱。