新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » 生物研究 » J Transl Med:石棉暴露引发恶性间皮瘤的新机制

J Transl Med:石棉暴露引发恶性间皮瘤的新机制

来源:生物谷 2014-12-10 11:01

2014年12月10日讯 /生物谷BIOON/ --长期以来一直认为,暴露于石棉产生的肿瘤是由单个细胞基因突变后,产生多个突变克隆所引起的。但一种新的假说发表在Journal of Translational Medicine期刊上,新假说认为它是由多种细胞突变引起的。

恶性间皮瘤是一种罕见的癌症形式,据估计每年在美国,恶性间皮瘤影响到3200人,其中大多数人在确诊后一年内死亡。这种癌症的主要原因是接触石棉,石棉主要在建筑施工中使用。石棉纤维的吸入导致炎症,即使在经过30-50年休眠后也可能会导致细胞突变。

大多数癌症被认为是单克隆的,其中所有的肿瘤细胞可以被追溯到一个单一的细胞突变。夏威夷癌症中心大学研究人员着手调查这是否是也适用于恶性间皮瘤,或者是否恶性间皮瘤是多克隆,其中多克隆是指肿瘤是两个或更多个突变细胞生长的结果。

在这项研究中,对间皮瘤妇女的14例肿瘤活组织检查中16个样品进行测定。这些测定结果与健康男性和女性来源的对照DNA样本(并且公知的是单克隆细胞系)进行比较,结果发现间皮瘤是多克隆的。

美国夏威夷大学Michele Carbone研究员说:我们的研究表明,恶性间皮瘤是多克隆肿瘤。这些发现对于未来研究,特别是对肿瘤治疗中的基因组药物有重要意义。这些结果表明,未来的方法应针对有不同类型突变的多克隆癌细胞,而不是一个单一的单克隆细胞。

Michele Carbone说:我们的研究结果强调,必须同时攻击多个不同的分子靶标,以尽量消除不同的恶性间皮瘤细胞克隆,因为每个癌细胞克隆可能携带了自己的一套独特的分子变化。(生物谷Bioon.com)

本文系生物谷原创编译整理,欢迎转载!转载请注明来源并附原文链接。谢谢!

Evaluation of clonal origin of malignant mesothelioma

Sabahattin Comertpay,et al.

Background
The hypothesis that most cancers are of monoclonal origin is often accepted as a fact in the scientific community. This dogma arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas, which originate as monoclonal tumors. The possible clonal origin of malignant mesothelioma (MM) has not been investigated. Asbestos inhalation induces a chronic inflammatory response at sites of fiber deposition that may lead to malignant transformation after 30-50 years latency. As many mesothelial cells are simultaneously exposed to asbestos fibers and to asbestos-induced inflammation, it may be possible that more than one cell undergoes malignant transformation during the process that gives rise to MM, and result in a polyclonal malignancy.

Methods and results
To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 16 biopsies from 14 women MM patients. Out of 16 samples, one was non-informative due to skewed Lyonization in its normal adjacent tissue. Fourteen out of the 15 informative samples revealed two electrophoretically distinct methylated HUMARA alleles, the Corrected Allele Ratio (CR) calculated on the allele peak areas indicating polyclonal origin MM.

Conclusions
Our results show that MM originate as polyclonal tumors and suggest that the carcinogenic “field effect” of mineral fibers leads to several premalignant clones that give rise to these polyclonal malignancies.

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库