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新变异的小细胞肺癌被发现

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)。
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%15%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3POU2F3,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POU2F3SCLC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2018626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。

Related Links:

冷泉港实验室>>> www.cshl.edu


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