新变异的小细胞肺癌被发现
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By LabMedica International staff writers Posted on 01 Aug 2018 |
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图片：一根支气管，被染成红色和蓝色的细胞是支气管上皮的一部分。这表明其中有一种罕见细胞（染成蓝绿色），应该是一种丛状细胞。科学家发现了起源于这些细胞的一种新型肺癌，它过表达POU2F3这种调节基因的蛋白，有望成为治疗的靶体（图片蒙冷泉港实验室惠赐）。
小细胞肺癌(SCLC)被普遍视为肺神经内分泌细胞的肿瘤；然而，这种病的一种变体缺少神经内分泌特征，最近的一篇论文对此做了描述。
SCLC是一种极度需要新药的癌症，它没有专门的疗法，经常很早就扩散。化疗、放疗和手术只能使6%的患者从确诊起存活五年，所有的肺癌病例中约10%到15%是SCLC。
美国纽约冷泉港实验室(www.cshl.edu)的科研人员与其他科学家合作，用专门领域的CRISPR筛查人类癌细胞系，认定转录因子(TF) POU 2类同源框蛋白3（POU2F3，又称SKN-1a/OCT-11）极度依赖一部分SCLC细胞系。分析人类SCLC样本发现，POU2F3只在变异的SCLC肿瘤里表达，这样的肿瘤不表达神经内分泌标志物，却表达化学感应细胞系的标志物，称作丛状细胞。
科研小组利用了染色质特征测定和RNA特征测定的检查，并提供证据证明POU2F3是SCLC变体的丛状细胞身份的主要调节者。另外，他们显示，大多数SCLC肿瘤可归为三种品系之一：表达POU2F3、无刚毛鳞甲同源物1(ASCL1)或神经元分化1(NEUROD1)。结果显示，POU2F3是细胞身份的决定因素，并且依赖SCLC的丛状细胞样变体，它可能反映以前未识别的起源细胞或者SCLC的转分化事件。
该研究的论文发表于2018年6月26日的《基因与发育》(Genes & Development)杂志。第一作者、博士后研究人员Yu-Han Huang博士说：“过去，我们把不同形式的SCLC混在一起，因为在显微镜玻片上它们看起来相似，但是现在我们的一些分子检验能轻松鉴别这些恶性病变。我们的成功表明，我们应该为它们设计单独的检查，找到针对不同类型肿瘤的疗法。”
冷泉港实验室>>> www.cshl.edu
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