Background

CTCF encodes 11-zinc finger protein which is implicated in multiple tumors including the carcinoma of the breast. The Present study investigates the association of CTCF mutations and their expression in breast cancer cases.

Methods

A total of 155 breast cancer and an equal number of adjacent normal tissue samples from 155 breast cancer patients were examined for CTCF mutation(s) by PCR-SSCP and automated DNA sequencing. Immunohistochemistry (IHC) method was used to analyze CTCF expression. Molecular findings were statistically analyzed with various clinicopathological features to identify associations of clinical relevance.

Results

Of the total, 16.1% (25/155) cases exhibited mutation in the CTCF gene. Missense mutations Gln > His (G > T) in exon 1 and silent mutations Ser > Ser (C > T) in exon 4 of CTCF gene were analyzed. A significant association was observed between CTCF mutations and some clinicopathological parameters namely menopausal status (p = 0.02) tumor stage (p = 0.03) nodal status (p = 0.03) and ER expression (p = 0.04). Protein expression analysis showed 42.58% samples having low or no expression (+), 38.0% with moderate (++) expression and 19.35% having high (+++) expression for CTCF. A significant association was found between CTCF protein expression and clinicopathological parameters include histological grade (p = 0.04), tumor stage (p = 0.04), nodal status (p = 0.03) and ER status (p = 0.04).

Conclusions

The data suggest that CTCF mutations leading to its inactivation significantly contribute to the progression of breast cancer.

中文翻译：

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CTCF基因突变和低表达与乳腺癌进展的关系。

背景

CTCF编码 11-锌指蛋白，该蛋白与包括乳腺癌在内的多种肿瘤有关。本研究调查了CTCF突变及其在乳腺癌病例中的表达的关联。

方法

通过 PCR-SSCP 和自动 DNA 测序对来自 155 名乳腺癌患者的 155 份乳腺癌和相同数量的相邻正常组织样本进行CTCF突变检查。使用免疫组织化学 (IHC) 方法分析 CTCF 表达。用各种临床病理学特征对分子发现进行统计分析，以确定临床相关性的关联。

结果

其中，16.1% (25/155) 的病例表现出CTCF基因突变。分析了CTCF基因外显子1中的错义突变Gln > His (G > T)和外显子4中的沉默突变Ser > Ser (C > T) 。观察到CTCF突变与一些临床病理学参数之间存在显着关联，即绝经状态 ( p  = 0.02) 肿瘤分期 ( p  = 0.03) 淋巴结状态 ( p  = 0.03) 和ER表达 ( p = 0.04)。蛋白质表达分析显示，42.58% 的样品具有低表达或无表达 (+)，38.0% 具有中度 (++) 表达，19.35% 具有高 (+++) 表达 CTCF。CTCF蛋白表达与临床病理参数之间存在显着关联，包括组织学分级（p  = 0.04）、肿瘤分期（p  = 0.04）、淋巴结状态（p  = 0.03）和ER状态（p  = 0.04）。

结论

数据表明，导致其失活的CTCF突变显着促进了乳腺癌的进展。