基于 NGS 的甲基化分析可区分 TCF3-HLF 和 TCF3-PBX1 阳性 B 细胞急性淋巴细胞白血病。
NGS-based methylation profiling differentiates TCF3-HLF and TCF3-PBX1 positive B-cell acute lymphoblastic leukemia.
机构信息
Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel 24105, Germany.
Channing Laboratory, Department of Medicine, Brigham & Women's Hospital & Harvard Medical School, Boston, MA 02115, USA.
出版信息
Epigenomics. 2018 Feb;10(2):133-147. doi: 10.2217/epi-2017-0080. Epub 2018 Jan 15.
AIM
To determine whether methylation differences between mostly fatal TCF3-HLF and curable TCF3-PBX1 pediatric acute lymphoblastic leukemia subtypes can be associated with differential gene expression and remission.
MATERIALS & METHODS: Five (extremely rare) TCF3-HLF versus five (very similar) TCF3-PBX1 patients were sampled before and after remission and analyzed using reduced representation bisulfite sequencing and RNA-sequencing.
RESULTS
We identified 7000 differentially methylated CpG sites between subtypes, of which 78% had lower methylation levels in TCF3-HLF. Gene expression was negatively correlated with CpG sites in 23 genes. KBTBD11 clearly differed in methylation and expression between subtypes and before and after remission in TCF3-HLF samples.
CONCLUSION
KBTBD11 hypomethylation may be a promising potential target for further experimental validation especially for the TCF3-HLF subtype.
目的
确定 TCF3-HLF（主要致命型）和 TCF3-PBX1（可治愈型）儿童急性淋巴细胞白血病亚型之间的甲基化差异是否与差异基因表达和缓解相关。
材料与方法
在缓解前后分别采集了 5 例（极为罕见）TCF3-HLF 患者和 5 例（非常相似）TCF3-PBX1 患者的样本，并采用简化代表性重亚硫酸盐测序和 RNA 测序进行分析。
结果
我们在亚型之间鉴定出了 7000 个差异甲基化 CpG 位点，其中 78%在 TCF3-HLF 中甲基化水平较低。基因表达与 23 个基因中的 CpG 位点呈负相关。KBTBD11 在 TCF3-HLF 样本的亚型之间、缓解前后的甲基化和表达上均有明显差异。
结论
KBTBD11 低甲基化可能是进一步实验验证的有前途的潜在靶点，特别是对 TCF3-HLF 亚型。
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