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首页> 外文期刊>Life sciences >Promoter hypermethylation of TMS1, BRCA1, ERalpha and PRB in serum and tumor DNA of invasive ductal breast carcinoma patients.
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Promoter hypermethylation of TMS1, BRCA1, ERalpha and PRB in serum and tumor DNA of invasive ductal breast carcinoma patients.

机译：浸润性导管癌患者血清和肿瘤DNA中TMS1，BRCA1，ERalpha和PRB的启动子甲基化过高。

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Breast cancer is fast emerging as the leading cancer amongst females, especially in younger age group in India; a large proportion of these tumors are often aggressive and ER and/or PR negative. Promoter methylation of genes involved in DNA repair and hormonal regulation may, in part, account for this behavior. To test this hypothesis methylation status of tumor suppressor genes TMS1, BRCA1, ERalpha and PRB was determined in invasive ductal carcinoma of breast and paired serum DNA. Of the 50 breast cancer patients investigated, 36/50 (72%) tumors and 32/50 (64%) paired sera showed methylation of at least one of these genes, while 17/50 (34%) tumors and 12/50 (24%) sera showed methylation of three genes. Methylation frequencies ranged from 24% for TMS1 to 63% for ERalpha. Significant association was observed between ERalpha and PRB methylation (p< or =0.001) and there was concordance between DNA methylation in tumor and serum for each gene. Immunohistochemical analysis showed no detectable expression ofERalpha, PRB and BRCA1 in 21/36 (58%), 20/36 (56%) and 23/36 (64%) tumors respectively; significant correlation was observed between promoter methylation and loss of protein expression confirming our hypothesis that promoter methylation is an important mechanism for transcriptional silencing of these genes in breast cancer in this population. This study also underscores the potential utility of DNA methylation based screening of serum (a surrogate for tumor DNA methylation) as a tool for detection of breast cancer.
机译：乳腺癌正在迅速崛起，成为女性中最主要的癌症，尤其是在印度的年轻人群中。这些肿瘤中很大一部分通常是侵袭性的，ER和/或PR阴性。参与DNA修复和激素调节的基因的启动子甲基化可能部分解释了这种行为。为了检验这一假设，确定了乳腺浸润性导管癌和配对血清DNA中抑癌基因TMS1，BRCA1，ERalpha和PRB的甲基化状态。在接受调查的50名乳腺癌患者中，有36/50（72％）肿瘤和32/50（64％）配对血清显示了至少一种这些基因的甲基化，而17/50（34％）肿瘤和12/50（ 24％的血清显示了三个基因的甲基化。甲基化频率范围从TMS1的24％到ERalpha的63％。在每个基因的ERalpha和PRB甲基化之间观察到显着关联（p <或= 0.001），并且肿瘤和血清中的DNA甲基化之间存在一致性。免疫组织化学分析未分别在21/36（58％），20/36（56％）和23/36（64％）肿瘤中检测到ERalpha，PRB和BRCA1的表达。在启动子甲基化和蛋白表达丧失之间观察到显着相关性，证实了我们的假设：启动子甲基化是该人群乳腺癌中这些基因转录沉默的重要机制。这项研究还强调了基于DNA甲基化的血清筛查（肿瘤DNA甲基化的替代物）作为检测乳腺癌的工具的潜在实用性。

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