Methylation alteration of SHANK1 as a predictive, diagnostic and prognostic biomarker for chronic lymphocytic leukemia.
Methylation alteration of SHANK1 as a predictive, diagnostic and prognostic biomarker for chronic lymphocytic leukemia.
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DOI：
10.18632/oncotarget.27080
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发表时间：
2019-08-13
期刊：
影响因子：
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通讯作者：
Zavattari, Patrizia
中科院分区：
文献类型：
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作者：
Loi, Eleonora;Moi, Loredana;Zavattari, Patrizia
慢性淋巴细胞白血病（CLL）是一种临床异质性疾病，其特征在于恶性B细胞的克隆性扩增。为了预测疾病的临床过程，迫切需要鉴定诊断生物标志物。异常的甲基化模式可以预测CLL的发展及其过程，是癌发生过程中非常早期的变化。我们的目的是确定CLL特异性甲基化模式，并评估所选基因的甲基化畸变是否与基因表达的变化相关。在这里，通过进行全基因组甲基化分析，我们确定了几个CLL特异性甲基化改变。我们集中在最改变的一个，在一个CpG岛位于体内的SHANK1基因，在我们的CLL病例相比，健康对照。这种甲基化改变在包括139个CLL和20个对照的更大队列中成功验证。我们还发现CLL患者中SHANK 1甲基化水平与淋巴细胞绝对计数，特别是CD 19 + B细胞之间呈正相关。此外，我们能够在诊断前几年收集的血液样本中检测到SHANK1甲基化的增加。总的来说，我们的研究结果表明，SHANK1 CpG岛的甲基化改变是CLL风险和诊断的生物标志物，也是肿瘤侵袭性的个性化定量。
Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by the clonal expansion of malignant B cells. To predict the clinical course of the disease, the identification of diagnostic biomarkers is urgently needed. Aberrant methylation patterns may predict CLL development and its course, being very early changes during carcinogenesis. Our aim was to identify CLL specific methylation patterns and to evaluate whether methylation aberrations in selected genes are associated with changes in gene expression. Here, by performing a genome-wide methylation analysis, we identified several CLL-specific methylation alterations. We focused on the most altered one, at a CpG island located in the body of SHANK1 gene, in our CLL cases compared to healthy controls. This methylation alteration was successfully validated in a larger cohort including 139 CLL and 20 control in silico samples. We also found a positive correlation between SHANK1 methylation level and absolute lymphocyte count, in particular CD19+ B cells, in CLL patients. Moreover, we were able to detect gains of methylation at SHANK1 in blood samples collected years prior to diagnosis. Overall, our results suggest methylation alteration at this SHANK1 CpG island as a biomarker for risk and diagnosis of CLL, and also in the personalized quantification of tumor aggressiveness.