Examination of IGF2 and H19 loss of imprinting in bladder cancer

Examination of IGF2 and H19 loss of imprinting in bladder cancer
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DOI:
10.1158/0008-5472.can-07-0329
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发表时间:
2007-11-15
期刊:
影响因子:
11.2
通讯作者:
Yang, Allen S.
Yang, Allen S.
中科院分区:
医学1区
文献类型:
--
作者:
Byun, Hyang-Min;Wong, Hui-Lee;Yang, Allen S.

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印记缺失(1,01)是癌症中常见的表观遗传事件,可作为某些癌症的早期生物标志物。为了更好地了解1,01,我们研究了41例膀胱肿瘤及其邻近正常膀胱粘膜。我们发现2/9(22.2%)例显示IGF 2的LOI,2/16(12.5%)例显示H19的LOI,如通过评估双等位基因表达的mRNA所确定的。此外,我们使用一种新的等位基因特异性焦磷酸测序法检测了IGF 2和H19差异甲基化区域(DMR)的等位基因特异性甲基化。我们发现DNA甲基化改变是DMR区域的常见发现(21/30,70%),但不能清楚地将DNA甲基化改变与通过双等位基因表达测量的LOI联系起来。膀胱癌中存在LOI和等位基因特异性DNA甲基化变化;然而,在将其用作表观遗传生物标志物之前,需要更好地了解LOI的生物学及其与DNA甲基化变化的关系。
Loss of imprinting (1,01) is a common epigenetic event in cancer and may serve as an early biomarker in some cancers. To obtain a better understanding of 1,01, we studied 41 bladder tumors and their adjacent normal bladder mucosa. We found 2/9 (22.2%) cases that displayed LOI of IGF2 and 2/16 (12.5%) that had LOI of H19, as determined by the evaluation of mRNA for biallelic expression. In addition, we examined allele-specific methylation of the differentially methylated regions (DMR) of IGF2 and H19 using a new allele-specific pyrosequencing assay. We found that DNA methylation changes were a common finding (21/30, 70%) in the DMR regions, but could not clearly link DNA methylation changes with LOI as measured by biallelic expression. LOI and allele-specific DNA methylation changes are present in bladder cancer; however, a better understanding of the biology of LOI and its relationship to DNA methylation changes is needed before its use as an epigenetic biomarker.