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NAT GENET:超级基因图谱对抗凶险的T型急性淋巴细胞白血病

2017-07-05 佚名 生物探索

7月3日,Nature子刊《Nature Genetics》在线发表了一篇针对一种恶性儿童血液肿瘤——T型急性淋巴细胞白血病(T-ALL)进行的首个最大规模的基因组测序成果。来自于美国圣犹大儿童医院和儿童肿瘤研究组等研究机构的科学家们对数百名T-ALL患者进行基因组测序,对结果进行一系列复杂分析后构建了前所未有的基因图谱。这一图谱为T型急性淋巴细胞白血病提供更多的治疗信息,挖掘了很多之前从未被发现

7月3日,Nature子刊《Nature Genetics》在线发表了一篇针对一种恶性儿童血液肿瘤——T型急性淋巴细胞白血病(T-ALL)进行的首个最大规模的基因组测序成果。来自于美国圣犹大儿童医院和儿童肿瘤研究组等研究机构的科学家们对数百名T-ALL患者进行基因组测序,对结果进行一系列复杂分析后构建了前所未有的基因图谱。

这一图谱为T型急性淋巴细胞白血病提供更多的治疗信息,挖掘了很多之前从未被发现的突变基因,有助于动物模型的而构建、新药的研发以及新致病机理的解析。

研究由圣犹大儿童医院病理学教授Charles Mullighan、儿童医院计算生物学部门主管Jinghui Zhang、费城儿童医院的Stephen Hunger带领完成。

T型急性淋巴细胞白血病

急性淋巴细胞白血病是最常见的儿童癌症,约90%的ALL儿童患者能够治愈,但是却存在复发的概率。其中,T-ALL占据15%的比例,免疫系统中的T细胞会因为多种突变而失去成熟及行使功能的能力。突变后的T细胞会在身体内累积,取代正常细胞。

通常,Notch信号通路、T细胞转录因子以及INK4/ARF肿瘤抑制基因是T-ALL的重要标记物,但是关于T-ALL的大规模基因组测序工作却从未被进行过。

构建基因图谱,挖掘到106个驱动基因

研究团队招募了264名儿童及年轻患者,对他们进行了基因组测试。文章一作、Jinghui Zhang课题组的博士后Yu Liu进行了多种基因组数据的复杂分析。他们共筛选到106个致病基因——这些基因突变会导致T细胞功能障碍,导致癌症。其中,有一半突变基因是最新发现与T-ALL有关联的。

研究人员分析了癌变的T细胞,并与那些因为治疗而维持正常状态的T细胞进行比较,从而为特定的治疗成功阻止特定致癌突变的机理提供有价值的线索。

癌症由突变基因驱动,这些基因表达的蛋白/酶参与重要信号通路。虽然癌症很有可能由最初的基因突变引发,但是这个突变位点会引发一系列其他突变,加剧癌症的发生和发展。新的基因组分析证实,T-ALL由已知信号通路中的突变驱动,包括JAK-STAT、Ras 和PTEN-PI3K。除了这些驱动突变之外,已知通路中存在更多导致病变的基因突变。

“这是首个全面、系统的大样本分析,揭示了很多具有生物学意义、有望成为药物靶点的新突变,具有很大的临床意义。” Mullighan表示,“白血病通常由多个基因突变导致。大多数之前的研究并没有获得足够多的基因组数据,用于筛选基因突变并寻找它们之间的关联性。现在我们挖掘到很多之前未被发现的突变位点。”

原始出处:
Yu Liu, John Easton,Ying Shao,et al,The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia.Nature Genetics (2017) doi:10.1038/ng.3909.

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    2018-06-13 liye789132251
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    2018-05-15 canlab
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    2018-03-23 cy0324
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    2017-07-07 Jackie Li

    学习

    0

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