Nat Metab:线粒体DNA突变,竟能降低癌症患者死亡风险

2021-07-13 “生物世界”公众号 “生物世界”公众号

2021年4月8日,美国纪念斯隆·凯特琳癌症研究中心的研究人员在 Nature Metabolism 期刊发表了题为:Respiratory complex and tissue lineage dr

线粒体(mitochondrion),是细胞的“能量工厂”,相当于细胞内的“发电厂”,线粒体内有一套独立于细胞核的遗传物质——线粒体DNA(mtDNA),人类线粒体DNA的长度为16569bp,拥有37个基因,编码13种蛋白,这些蛋白都参与细胞的能量代谢。

在人类衰老和一系列疾病中,都涉及线粒体DNA(mtDNA)的表达改变,而线粒体DNA(mtDNA)的突变更是会直接导致数十种严重的遗传疾病。

2021年4月8日,美国纪念斯隆·凯特琳癌症研究中心的研究人员在 Nature Metabolism 期刊发表了题为:Respiratory complex and tissue lineage drive recurrent mutations in tumour mtDNA 的研究论文。

该研究发现,线粒体DNA突变与结直肠癌患者生存率显着提高有关,具体来说,肿瘤中线粒体DNA突变的存在及不同类型突变,导致结直肠癌患者的癌症死亡风险降低了57%至93%。此外,该研究还发现,线粒体DNA突变在多种癌症类型中普遍存在。

这项新研究揭示了线粒体DNA突变对癌症的影响,而这一现象几十年以来一直被被人们所忽略,这一发现也将对癌症患者的治疗产生巨大影响,可以根据患者癌细胞中线粒体DNA的状态,改变建议的治疗方法。

虽然我们的绝大多数DNA都位于细胞核的中心,但线粒体中也有一些DNA,也就是线粒体DNA(mtDNA),这些线粒体是细胞中的“能量工厂”,可帮助我们将糖转化为能量,供给细胞和人体消耗。

正如我们的细胞核DNA会出现随机突变一样,线粒体中的DNA也会发生突变。众所周知,癌细胞中会出现线粒体DNA突变,但是这些癌细胞中的线粒体DNA突变,对于癌症的发展和治疗有何作用,目前仍然知之甚少。

为了回答这些问题,美国纪念斯隆·凯特琳癌症研究中心和英国格拉斯哥大学癌症科学研究所的研究人员展开合作,整理和分析来自最大的肿瘤样本数据库TCGA的数据,其中包括线粒体基因组数据和患者相应的临床结果。

通过分析344名结直肠癌患者的数据,研究团队将线粒体突变组与癌症生存率进行了对比,结果发现,在调整了影响癌症风险的年龄等变量之后,线粒体突变的存在与结直肠癌致死风险降低57%至93%有关,具体取决于线粒体DNA突变的类型——截短突变(Truncating)和意义不定突变(VUS)。

为了确定更广泛的癌症中线粒体突变的普遍性。研究团队从23种癌症类型的10000多个肿瘤样本中查看了现有数据,以寻找经常重复出现的线粒体突变。结果表明,60%的肿瘤样本中存在线粒体DNA突变。

这些结果表明,不只是在结直肠癌中,线粒体DNA突变还可能在其他类型癌症的生存中发挥作用。还需要进一步研究,以了解线粒体DNA突变在不同癌症中的广泛影响,并深入研究其背后的生物学基础。

这项新研究揭示了线粒体DNA突变对癌症的影响,而这一现象几十年以来一直被被人们所忽略,这一发现也将对癌症患者的治疗产生巨大影响,可以根据患者癌细胞中线粒体DNA的状态,改变建议的治疗方法。

这项研究也提醒了我们,对于癌症,我们还有很多未涉足的领域,这些领域将为癌症研究带来哪些潜力,我们拭目以待。

原始出处:

Gorelick,A.N.,Kim,M.,Chatila,W.K. et al. Respiratory complex and tissue lineage drive recurrent mutations in tumour mtDNA. Nat Metab 3, 558–570 (2021). https://doi.org/10.1038/s42255-021-00378-8.

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time=2021-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=998892, encodeId=721d99889211, content=学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210611/f7616d040e6842afb334fb7dc7fe70d5/b02af0ca19f148e6988b157b7f6cd6e8.jpg, createdBy=b4eb5518910, createdName=亭儿789, createdTime=Mon Jul 12 21:07:49 CST 2021, time=2021-07-12, status=1, ipAttribution=)]
    2021-09-12 guojianrong
  4. 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time=2021-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=998892, encodeId=721d99889211, content=学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210611/f7616d040e6842afb334fb7dc7fe70d5/b02af0ca19f148e6988b157b7f6cd6e8.jpg, createdBy=b4eb5518910, createdName=亭儿789, createdTime=Mon Jul 12 21:07:49 CST 2021, time=2021-07-12, status=1, ipAttribution=)]
    2021-10-24 一闲
  5. 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time=2021-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=998892, encodeId=721d99889211, content=学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210611/f7616d040e6842afb334fb7dc7fe70d5/b02af0ca19f148e6988b157b7f6cd6e8.jpg, createdBy=b4eb5518910, createdName=亭儿789, createdTime=Mon Jul 12 21:07:49 CST 2021, time=2021-07-12, status=1, ipAttribution=)]
    2021-10-09 liye789132251
  6. 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  7. 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  8. 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  9. 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