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首页 » 癌症研究 » Clinical Epigenetics:DNA甲基化检测或可帮助预测乳腺癌复发

Clinical Epigenetics:DNA甲基化检测或可帮助预测乳腺癌复发

来源:生物谷 2015-09-25 09:23

2015年9月25日讯/生物谷BIOON/-发表在今天《临床实验胚胎学》杂志上的新研究表明有一种简单的血液测试方法可以确定癌症侵犯其他器官如肺、骨头或大脑等疾病复发的风险。这样的测试对改善所有类型的女性乳腺癌会产生深远影响,这种疾病会影响八分之一的女性。

在研究中,翻译基因组学研究院(TGen)的研究人员确定了21 DNA甲基化热点——随着30亿化学碱基的DNA甲基化水平增加,可能有转移性乳腺癌的存在。

“这些发现可能导致一个高度敏感的血液测试面板-一种液体活检可以帮助改善乳腺癌患者的治疗。”Bodour Salhia博士说。

“这种21-gene是一种潜在的生物标志物,可能表明患者乳房或身体的其它部位癌症复发处于高危状态,患者可能受益于附加的治疗来消除疾病复发的可能。”Salhia博士说。“这将是至关重要的信息,因为他们会考虑术后持续治疗或完成每一轮化疗的情况。”

生物标志物是指标分子,如蛋白质或DNA,他们在血液、体液或组织样本中是可测的,可以用来诊断或衡量一个特定疾病或给定治疗的影响。

利用全基因组测序,研究人员从40例转移性乳腺癌患者的血液样本中寻找生物标记的DNA游离链(cfDNA)循环池,并将他们与40例健康个体和40例无病乳腺癌复发的幸存者进行比较。

研究结果表明,尽管来自现行的其他基因特征的巨大数量信息是可用的,但没有一个可以精确地预测个体的临床过程,它们依赖于组织存在,出现在一个单一的时间点。有患者认为用标准治疗高风险疾病做得很好,且从不复发。

相比之下,TGen研究发现 21基因被“差异甲基化”——这意味着他们可能会改变甲基化水平——与健康个体和癌症幸存者相比,所有这些在转移性乳腺癌患者体内会持续升高。

下一步我们会确证使用个体样本的结果。(生物谷Bioon.com)

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Whole-genome bisulfite sequencing of cell-free DNA identifies signature associated with metastatic breast cancer

Christophe Legendre†, Gerald C. Gooden†, Kyle Johnson, Rae Anne Martinez, Winnie S. Liang and Bodour Salhia*

A number of clinico-pathological criteria have been established as breast cancer prognostic markers to determine risk of recurrence and stratify patients into high- and low-risk groups. The likelihood of distant metastasis increases with tumor size, the presence and number of lymph-node involvement (≥4 nodes have a higher recurrence risk), lack of estrogen receptor (ER) expression, over-expression of Her2, a high proliferative index, lymphovascular invasion, and loss of histopathological differentiation [1]. Molecular profiles have improved our ability to determine the need of chemotherapy for those individuals who are deemed high-risk. The most widely used multigene classifiers include the 21-gene Oncotype Dx signature (Genomic Health, USA), the 70-gene MammaPrint signature (Agendia, Netherlands), the 76-gene Rotterdam signature, and the PAM50 intrinsic classifier (NanoString, USA) [2]. Despite the huge quantity of information gleaned from these gene signatures, none can precisely predict the clinical course of an individual and rely on the presence of tissue at a single time point. Therefore, they are not able to monitor a patient’s risk status after completion of therapy due to residual disease. Even with the clinico-pathological features, there are patients deemed high-risk who do very well with standard therapy and never experience a recurrence and patients with low-risk profiles who still die of breast cancer. There also remains a risk of recurrence even after the most effective chemotherapy agents are administered to high-risk patients. We report a 21-gene DNA hypermethylation signature, detectable in the circulation of MBC patients, which maybe useful in the pre-macrometastatic setting to indicate patients at a high risk of recurrence.

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