Sharma Preeti, Bhunia Shushruta, Poojary Satish S, Tekcham Dinesh S, Barbhuiya Mustafa Ahmed, Gupta Sanjiv, Shrivastav Braj Raj, Tiwari Pramod Kumar
Molecular and Human Genetics Division, Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, 474011, India.
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, MD, Baltimore, USA.
Tumour Biol. 2016 Nov;37(11):14687-14699. doi: 10.1007/s13277-016-5355-9. Epub 2016 Sep 14.
Promoter methylation in various tumor suppressor genes is reported to influence gallbladder carcinogenesis. Here, we aimed to identify methylation status in gallbladder cancer (GBC) by performing a comprehensive genome-wide DNA methylation profiling. The methylation status of 485,577 CpG sites were investigated using Illumina's Infinium Human Methylation 450 BeadChip array in 24 tissues (eight each of tumor, adjacent non-tumor, and gallstone). About 33,443 differentially methylated sites (DMRs) were obtained in the whole human genome, of which 24,188 (72 %) were hypermethylated and 9255 (28 %) were hypomethylated. The data also revealed that majority of the DMRs are localized on the proximal promoter region [Transcription start sites (TSS200, TSS1500) and 5' untranslated region (5'UTR)] and first exon. Exclusion of first exon detected a total of 10,123 (79 %) hypermethylated and 2703 (21 %) hypomethylated sites. Comparative analysis of the later with our differential proteomics data resulted in identification of 7 hypermethylated or down-regulated (e.g., FBN1, LPP, and SOD3) and 61 hypomethylated or up-regulated markers (e.g., HBE1, SNRPF, TPD52) for GBC. These genes could be further validated on the basis of their methylation/expression status in order to identify their utility to be used as biomarker/s for early diagnosis and management of GBC.
据报道，各种肿瘤抑制基因中的启动子甲基化会影响胆囊癌的发生。在此，我们旨在通过进行全面的全基因组DNA甲基化分析来确定胆囊癌（GBC）中的甲基化状态。使用Illumina的Infinium Human Methylation 450 BeadChip阵列在24个组织（肿瘤、相邻非肿瘤和胆结石组织各8个）中研究了485,577个CpG位点的甲基化状态。在整个人类基因组中获得了约33,443个差异甲基化位点（DMR），其中24,188个（72%）为高甲基化，9255个（28%）为低甲基化。数据还显示，大多数DMR位于近端启动子区域[转录起始位点（TSS200、TSS1500）和5'非翻译区（5'UTR）]和第一外显子上。排除第一外显子后，共检测到10,123个（79%）高甲基化位点和2703个（21%）低甲基化位点。将后者与我们的差异蛋白质组学数据进行比较分析，确定了7个GBC的高甲基化或下调标志物（如FBN1、LPP和SOD3）以及61个低甲基化或上调标志物（如HBE1、SNRPF、TPD52）。这些基因可根据其甲基化/表达状态进一步验证，以确定其作为GBC早期诊断和管理生物标志物的效用。
