Nat Commun:甲基化测序捕捉三阴性乳腺癌表观遗传特性

2015-02-05 佚名 生物谷

近日,一篇刊登在国际杂志Nature Communications上的研究报告中,来自澳大利亚悉尼加文医学研究所(Garvan Institute of Medical Research)的科学家们通过将乳腺癌患者机体的乳腺癌甲基化组同健康个体进行比较从而绘制出了一种新型的基因组图谱,其可以帮助揭示DNA如何被甲基化基团进行修饰,即DNA的甲基化过程。 本文研究揭示了乳腺癌细胞主要活检组织中

近日,一篇刊登在国际杂志Nature Communications上的研究报告中,来自澳大利亚悉尼加文医学研究所(Garvan Institute of Medical Research)的科学家们通过将乳腺癌患者机体的乳腺癌甲基化组同健康个体进行比较从而绘制出了一种新型的基因组图谱,其可以帮助揭示DNA如何被甲基化基团进行修饰,即DNA的甲基化过程。

本文研究揭示了乳腺癌细胞主要活检组织中不同的甲基化模式,其可以有效揭示患者的预后情况;三阴性乳腺癌在所有乳腺癌中占到了15%至20%,患该类乳腺癌的患者相比其它乳腺癌患者的复发风险和死亡率都较高;三阴性乳腺癌患者往往分为两类:第一类是不管是否进行治疗患者在3-5年内就会死亡;第二类是平均比非三阴性乳腺癌患者存活时间更长的患者群(在诊断后至少可以存活8年)。

目前并没有可靠的方法来对上述两类三阴性乳腺癌进行区分,而临床医生往往依据肿瘤的尺寸、扩散程度以及淋巴结的渗透性来决定患者应该被分为高风险类还是低风险类中。Susan Clark教授说道,文章中我们对三阴性乳腺癌患者的组织样本和配对的正常样本进行全基因组甲基化捕捉测序,同时进行新一代的测序来确定癌症在DNA甲基化中的特异性改变。

这项研究首次调查了三阴性乳腺癌的甲基化组及其和疾病预后的关联情况,目前在进行该疾病的有效管理上仍然缺乏相关的依据,由于缺少强大的检测诊断工具,很多女性都存在治疗过度的情况。研究者指出,根据肿瘤的表观遗传特性对其进行分类,我们就可以随着时间对选择性的乳腺癌群体进行追踪,及时监测患者对不同疗法的反应情况。

目前研究者Clare Stirzaker及其同事开发出的新型方法可以对归档的组织进行DNA提取来对甲基化组进行测序,从而实现将患者的甲基化模式同其疾病预后相联系起来。开发一种甲基化的测序技术也可以帮助研究者进行更多深入的研究。最后研究者表示,本文研究或为后期开发乳腺癌的新型诊断工具提供一定的帮助和线索。

原始出处

Stirzaker C1, Zotenko E1, Song JZ2, Qu W2, Nair SS1, Locke WJ1, Stone A1, Armstong NJ3, Robinson MD4, Dobrovic A5, Avery-Kiejda KA6, Peters KM7, French JD8, Stein S9, Korbie DJ10, Trau M11, Forbes JF12, Scott RJ13, Brown MA7, Francis GD14, Clark SJ1.Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value.Nat Commun. 2015 Feb 2

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    2015-07-03 liuli5079
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    2015-02-16 windmilL1989

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    2015-10-07 liye789132251
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    2015-02-07 xlysu

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《癌症研究》杂志日前在线发表了上海交通大学基础医学院王建华团队的最新研究成果。相关专家认为,该研究为临床上寻找三阴性乳腺癌合适的治疗靶点具有重要意义。 据了解,HIC1是一种肿瘤抑制因子,位于人类第17号染色体短臂。该基因在很多实体肿瘤组织中存在表达沉默的现象。王建华团队从表观遗传学修饰的角度,在阐明HIC1调控前列腺癌发展、转移中的作用机制后,又发现了HIC1的表达沉默只发生在三阴性乳腺癌中。