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Epstein Barr virus: a prime candidate of breast cancer aetiology in Sudanese patients

机译:爱泼斯坦巴尔病毒:苏丹患者乳腺癌病因的主要候选者

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Breast cancer is the commonest cancer in Sudanese women. Reported genetic alterations in the form of mutations in tumor suppressors are low in frequencies and could not explain the peculiarities of the diseases including its focal nature. Potential contributors disease aetiology include oncogenic viruses such as Epstein-Barr virus (EBV), an established culprit of nasopharyngeal carcinoma, one of the most frequent cancers in Sudan. In this study, DNA was extracted from malignant tissue samples and healthy tumour-free tissue from the same breast. Polymerase chain Reaction (PCR) was used to amplify two genes encoding for EBV viral proteins. The presence of Epstein-Barr virus and its cellular localization was confirmed by in situ hybridization (ISH) for Epstein-Barr encoded small RNAs (EBERs). Given the reported low frequency of mutations in BRCA1 and BRCA2 in Sudanese breast cancer patients, the methylation status of six tumor suppressor genes was investigated using methylation specific PCR. EBV genome was detected in 55.5% (n?=?90) of breast cancer tissues as compared to 23% in control tissue samples (p?=?0.0001). Using ISH, EBV signal was detected in all 18 breast cancer biopsies examined while all five normal breast tissue biopsies tested were negative for EBV. Of six tumour suppressor genes investigated BRCA1, BRCA2, and p14 appeared to be under strong epigenetic silencing. In conclusion, we present evidence of a strong association between EBV and breast carcinoma in Sudanese patients, and considerable epigenetic silencing of tumor suppressors that may likely be an outcome or an association with viral oncogenesis.
机译:乳腺癌是苏丹女性中最常见的癌症。据报道,抑癌基因突变形式的遗传改变发生频率低,不能解释疾病的特殊性,包括其局灶性。潜在的致病病因包括致癌病毒,例如爱泼斯坦-巴尔病毒(EBV),这是鼻咽癌的确定元凶,鼻咽癌是苏丹最常见的癌症之一。在这项研究中,从同一乳房的恶性组织样本和无肿瘤的健康组织中提取DNA。聚合酶链反应(PCR)用于扩增编码EBV病毒蛋白的两个基因。通过针对爱泼斯坦-巴尔编码的小RNA(EBER)的原位杂交(ISH)证实了爱泼斯坦-巴尔病毒的存在及其细胞定位。鉴于苏丹乳腺癌患者中BRCA1和BRCA2突变的报道频率较低,因此使用甲基化特异性PCR研究了六个肿瘤抑制基因的甲基化状态。在55.5%(n?=?90)的乳腺癌组织中检测到EBV基因组,而在对照组织样本中检测到EBV基因组的比例为23%(p?=?0.0001)。使用ISH,在检查的所有18例乳腺癌活检中均检测到EBV信号,而所测试的所有5例正常乳腺组织活检均显示EBV阴性。在研究的六个肿瘤抑制基因中,BRCA1,BRCA2和p14似乎处于强表观遗传沉默之下。总而言之,我们提供了证据,证明苏丹患者中EBV与乳腺癌之间有很强的关联性,并且肿瘤抑制因子有大量的表观遗传沉默,这可能是结局或与病毒致癌作用有关。

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