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Nature Genet:儿童侵袭性神经母细胞瘤致病基因被发现

2012-12-14 银子 摘编 医学论坛网

  来自约翰霍普金斯大学Kimmel癌症中心和费城儿童医院(CHOP)的科学家们发表在12月2日的《自然·遗传学》(Nature Genetics)杂志上的一项研究结果表明:在对74个儿童神经母细胞瘤进行全基因组测序后,ARID1A和ARID1B两个基因发生改变的患儿相比无此基因改变的患儿生存期缩短了四分之三。这一发现有可能最终导致早期确认患有侵袭性神经母细胞瘤的儿童,他们或许需要接受其他的治疗。

  来自约翰霍普金斯大学Kimmel癌症中心和费城儿童医院(CHOP)的科学家们发表在12月2日的《自然·遗传学》(Nature Genetics)杂志上的一项研究结果表明:在对74个儿童神经母细胞瘤进行全基因组测序后,ARID1A和ARID1B两个基因发生改变的患儿相比无此基因改变的患儿生存期缩短了四分之三。这一发现有可能最终导致早期确认患有侵袭性神经母细胞瘤的儿童,他们或许需要接受其他的治疗。

脑

  神经母细胞瘤累及全身神经组织,是最常见的一种儿童恶性实体瘤。约翰霍普金斯大学癌症生物学计划联合主任、肿瘤学教授Victor Velculescu 博士说:“这些癌症具有广泛的临床结局,一些治愈的机会很高,而另一些则是相当致命的。出现这种预后多样性,部分原因可能是由于ARID1A和ARID1B基因的改变。”

  Velculescu说在以往其他的神经母细胞瘤基因测序研究中没有发现这些强大的“恶棍”(bully)基因。新研究能鉴别出它们,很有可能是因为约翰霍普金斯大学CHOP的研究人员采用测序和分析方法,除找到了单个碱基对序列的改变,还筛查了DNA更大的结构重排。

  在本研究的74个肿瘤中,有71个进行了重排和碱基对改变分析。研究人员在过去显示与神经母细胞瘤有关联的多个基因,包括ALK和MYCN基因中发现了癌症特异性的突变。他们还发现71名患者中8人有ARID1A和ARID1B基因的改变,这两个基因通常情况下通过调控DNA折叠方式来影响蛋白质合成。具有ARID1A和ARID1B基因改变的儿童平均生存期只有386天,相比之下没有这些遗传变异的儿童则达到1689天,两者相差甚远。然而除一人之外,所有这些患者均死于侵袭性疾病,包括一名被认为治愈机会很高的神经母细胞瘤患儿。

  在本研究中,科学家们还检测和监控了四名患者血液中神经母细胞瘤特异性的遗传改变,并将确定了这些调查结果与疾病进程之间的相互关联。在血液中寻找癌症特异性的改变,可能有助于临床医生监控患者的复发情况,确定手术后体内是否还有残留癌细胞。

  约翰霍普金斯大学CHOP研究小组计划在更大规模组群患者中开展进一步地研究,以证实ARID1A-ARID1B与预后相关。

  原文链接:Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma

    

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    2013-04-12 cy0324
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    2013-11-03 liye789132251
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    2013-07-19 canlab
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    2012-12-16 sunyl07
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