tw4ld6 发表于 2024-6-12 19:20:26

最全癌症驱动基因全景图：66种癌症中的568个致癌基因汇总


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      <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">撰文 |&nbsp;王聪</p>
    </span><span style="color: black;">编辑&nbsp;|&nbsp;nagashi</span><span style="color: black;">排版&nbsp;| 水成文</span><strong style="color: blue;">癌症</strong><span style="color: black;">是一大类<span style="color: black;">疾患</span>，其特征在于基因组中的突变或其他改变<span style="color: black;">引起</span>细胞生长不受<span style="color: black;">掌控</span>。</span><span style="color: black;">肿瘤可<span style="color: black;">显现</span>数百至数千个突变，但<span style="color: black;">仅有</span><span style="color: black;">少许</span>几个对其致瘤能力至关<span style="color: black;">要紧</span>。</span><span style="color: black;">这些<span style="color: black;">重要</span>突变影响癌症驱动基因的功能。</span><span style="color: black;">寻找<span style="color: black;">拥有</span>这种癌症驱动突变的基因是癌症<span style="color: black;">科研</span>的<span style="color: black;">重点</span><span style="color: black;">目的</span>之一。</span><span style="color: black;">2020年8月10日，西班牙巴塞罗那科学技术<span style="color: black;">科研</span>所的<span style="color: black;">科研</span>团队在</span><strong style="color: blue;"><span style="color: black;">Nature Reviews Cancer&nbsp;</span></strong><span style="color: black;">杂志<span style="color: black;">发布</span>了题为：</span><span style="color: black;">A compendium of mutational cancer driver genes</span><span style="color: black;">&nbsp;的论文。</span><span style="color: black;"><span style="color: black;">经过</span>对来自<strong style="color: blue;">66种癌症</strong>的<strong style="color: blue;">28076个肿瘤样本</strong>的基因组进行分析，</span><span style="color: black;"><strong style="color: blue;">鉴定了568个癌症驱动基因</strong></span><span style="color: black;">。<strong style="color: blue;">这是</strong></span><span style="color: black;"><strong style="color: blue;">迄今为止癌症驱动基因最完整全景图</strong></span><span style="color: black;">。<span style="color: black;">日前</span>该<span style="color: black;">科研</span>数据已在 <strong style="color: blue;">IntOGen</strong> 平台更新。</span><img src="https://mmbiz.qpic.cn/mmbiz_png/HO0Z9pUcnJmVxCFdFeMliarSTgVtic66iblibHdL1kunZKsYeYIxxNzIVnVXIYOxyO8kPia4NU2WPr2VG72iaqwq0dQg/640?wx_fmt=png&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/HO0Z9pUcnJmVxCFdFeMliarSTgVtic66iblzKWarjDvRmvXE8kmdCLPa422XEVxhGtiaWPD3vvHEpc7Z4OPthAHzOg/640?wx_fmt=jpeg&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;"><span style="color: black;">点击查看大图</span><span style="color: black;"><span style="color: black;">科研</span>人员对来自<strong style="color: blue;">66种癌症</strong>的<strong style="color: blue;">28076个肿瘤样本</strong>进行了广泛的计算分析，并确定了568个癌症驱动基因。这些<span style="color: black;">重要</span>基因在调控细胞生长，细胞周期和DNA复制等方面起特定<span style="color: black;">功效</span>。</span><span style="color: black;">这些基因的突变赋予恶性细胞快速<span style="color: black;">没</span>休止繁殖，逃避免疫系统和其他防御系统，扩散和侵袭其他组织，以及为其<span style="color: black;">自己</span>利益而改变环境的能力。</span><span style="color: black;"><span style="color: black;">经过</span>鉴定这568种癌症驱动基因，<span style="color: black;">科研</span>人员观察到<strong style="color: blue;">大<span style="color: black;">都数</span>基因<span style="color: black;">拥有</span>高度特异性，并且其突变仅能触发几种肿瘤类型</strong>。</span><span style="color: black;"><span style="color: black;">然则</span>，<span style="color: black;">亦</span>有一小部分癌症驱动基因功能强大，<strong style="color: blue;">TP53</strong>、<strong style="color: blue;">PIK3CA</strong>、<strong style="color: blue;">KMT2C</strong>、<strong style="color: blue;">ARID1A</strong>、<strong style="color: blue;">KMT2D</strong>、<strong style="color: blue;">LRP1B</strong>、<strong style="color: blue;">PTEN</strong>、<strong style="color: blue;">RB1</strong>、<strong style="color: blue;">FAT4</strong>、<strong style="color: blue;">KRAS</strong>，这10个基因<span style="color: black;">每一个</span>的突变都能<span style="color: black;">引起</span>20多种不同类型的癌症，其中最夸张的<span style="color: black;">便是</span>大名鼎鼎的&nbsp;<strong style="color: blue;">TP53&nbsp;</strong>基因，其突变<span style="color: black;">引起</span>的癌症超过50种。</span><img src="https://mmbiz.qpic.cn/mmbiz_png/HO0Z9pUcnJmVxCFdFeMliarSTgVtic66iblfxkk5u4ZQHsxUfAo5sBwf8yfSVR87wCqODY0vVWhcMHSUuEticONang/640?wx_fmt=png&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;"><span style="color: black;">尽管自从首次<span style="color: black;">发掘</span>癌症驱动基因<span style="color: black;">败兴</span>，<span style="color: black;">科研</span>人员就认识到了它们<span style="color: black;">拥有</span>不同程度的特异性，<span style="color: black;">然则</span>有了这个癌症驱动基因图谱，就<span style="color: black;">能够</span><span style="color: black;">没</span>偏见地<span style="color: black;">处理</span>这个问题。</span><span style="color: black;">之前的<span style="color: black;">科研</span><span style="color: black;">显示</span>，癌症平均由四种<span style="color: black;">重要</span>的癌症驱动基因平均<span style="color: black;">导致</span>。有些肿瘤仅由一种基因突变<span style="color: black;">引起</span>，而有些肿瘤，例如结直肠癌和子宫肿瘤等，10多种基因突变均可<span style="color: black;">引起</span>。</span><span style="color: black;"><span style="color: black;">另外</span>，其他基因组改变，例如<strong style="color: blue;">结构突变</strong>、<strong style="color: blue;">基因拷贝数改变</strong>以及<strong style="color: blue;">基因组非编码区突变</strong><span style="color: black;">亦</span>有助于肿瘤<span style="color: black;">出现</span>。</span><img src="https://mmbiz.qpic.cn/mmbiz_png/HO0Z9pUcnJmVxCFdFeMliarSTgVtic66iblcCWbibHxkVMb2WSvoPc1EkGzic9yQCoDs6Yv7bb1ct1xs7KALdpPaialg/640?wx_fmt=png&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;"><span style="color: black;">在癌症基因组学<span style="color: black;">起始</span>之前，<span style="color: black;">专家</span>们<span style="color: black;">已然</span>鉴定了几十个癌症驱动基因，<span style="color: black;">这里</span>后的二三十年里，<span style="color: black;">专家</span>们<span style="color: black;">持续</span>很如<span style="color: black;">科研</span>并表征了这些基因的功能。</span><span style="color: black;">而相比之下，在对<span style="color: black;">第1</span>个肿瘤基因组进行测序<span style="color: black;">败兴</span>不到二十年的时间里，<span style="color: black;">专家</span>们<span style="color: black;">已然</span><span style="color: black;">发掘</span>了数百种癌症驱动基因。</span><strong style="color: blue;"><span style="color: black;">DNA测序技术</span></strong><span style="color: black;">的进步和<strong style="color: blue;">生物信息学<span style="color: black;">办法</span></strong>的发展，使得<span style="color: black;">发掘</span>癌症驱动基因的速度越来越快。这<span style="color: black;">亦</span><span style="color: black;">引起</span>了</span><span style="color: black;"><strong style="color: blue;">癌症驱动基因的数量与人类已表征的癌症驱动基因数量之间存在了巨大的知识鸿沟。</strong></span><span style="color: black;">这<span style="color: black;">亦</span>在<span style="color: black;">必定</span>程度上<span style="color: black;">寓意</span>着，<strong style="color: blue;">尽快全面解析这568个癌症驱动基因驱动肿瘤<span style="color: black;">出现</span>发展，缩小这些知识鸿沟，是短期内癌症基因组学<span style="color: black;">科研</span>的重大挑战和<span style="color: black;">奋斗</span>方向</strong>。</span><span style="color: black;">该<span style="color: black;">科研</span>的领导者&nbsp;</span><span style="color: black;"><strong style="color: blue;">Nuria Lopez-Bigas</strong></span><span style="color: black;"><span style="color: black;">暗示</span>：“癌症驱动基因汇编为临床和<span style="color: black;">基本</span><span style="color: black;">科研</span><span style="color: black;">行业</span>的癌症<span style="color: black;">科研</span>人员<span style="color: black;">供给</span>了至关<span style="color: black;">要紧</span>的知识，并且对临床决策<span style="color: black;">拥有</span><span style="color: black;">要紧</span>影响。<span style="color: black;">倘若</span><span style="color: black;">咱们</span><span style="color: black;">晓得</span>肿瘤的致癌能力依赖于一种特定的蛋白质，<span style="color: black;">那样</span><span style="color: black;">科研</span>人员就能够会采用经过<span style="color: black;">准许</span>的靶向疗法，例如抗体或其他阻碍其功能的<span style="color: black;">控制</span>剂来治疗癌症。”</span><img src="https://mmbiz.qpic.cn/mmbiz_jpg/HO0Z9pUcnJmVxCFdFeMliarSTgVtic66ibl1xOxgVphaLiaEAX47rWvSL3PyYRTk6RAQicfiaia8zibsd1Ek8bE8AGEYicg/640?wx_fmt=jpeg&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;"><span style="color: black;">该项目的领导者——Nuria Lopez-Bigas</span><strong style="color: blue;"><span style="color: black;">参考链接：</span></strong><span style="color: black;">https://www.nature.com/articles/s41568-020-0290-x</span><span style="color: black;">https://www.intogen.org/search</span><a style="color: black;"><span style="color: black;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/HO0Z9pUcnJkTCGeqkeibdQaazyubCoBqs17tgGSP6Fty5rk8WImUxr4EkwhGQTDMK8n214Ob0DUNRIEUTA5pibCg/640?wx_fmt=jpeg&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;"></span></a><a style="color: black;"><span style="color: black;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/HO0Z9pUcnJngTL4PGbVgmibuW652j9uf16uQHd2zj4gs8BLbskGzta7JG2c3dyXSiaZs80eYSQib7Y3GbQAlN2c6Q/640?wx_fmt=jpeg&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;"></span></a><img src="https://mmbiz.qpic.cn/mmbiz_png/73icnXvmN7wOI0rvtgpcAvoymzwXc4GsnicX7nxUa21NoWg2J48JaZ95yswdzic3MZ3Hagz97n5zdXiaMtm7ic36oTA/640?wx_fmt=png&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; 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