Evaluation of clonal origin of malignant mesothelioma
Evaluation of clonal origin of malignant mesothelioma
复制标题
DOI：
10.1186/s12967-014-0301-3
复制
发表时间：
2014-12-04
影响因子：
7.4
通讯作者：
Carbone, Michele
中科院分区：
文献类型：
--
作者：
Comertpay, Sabahattin;Pastorino, Sandra;Carbone, Michele
背景：大多数癌症都是单克隆起源的假设在科学界通常被接受为事实。这一教条产生于几十年前，主要来自对造血系统恶性肿瘤和肉瘤的研究，它们起源于单克隆肿瘤。恶性间皮瘤（MM）可能的克隆起源尚未得到研究。吸入石棉会在纤维沉积部位诱发慢性炎症反应，潜伏 30-50 年后可能导致恶性转化。由于许多间皮细胞同时暴露于石棉纤维和石棉引起的炎症，因此在产生 MM 的过程中可能有不止一个细胞发生恶性转化，并导致多克隆恶性肿瘤。 方法和结果：为了研究 MM 的克隆模式，我们使用 HUMARA（人类雄激素受体）测定法检查了 14 名女性 MM 患者的 16 个活检组织。在 16 个样本中，有一个样本由于其正常邻近组织中的 Lyonization 不正确而无法提供信息。 15 个信息样本中的 14 个显示出两个电泳不同的甲基化 HUMARA 等位基因，根据等位基因峰面积计算的校正等位基因比率 (CR) 表明多克隆起源 MM。结论：我们的结果表明 MM 起源于多克隆肿瘤，并表明矿物纤维的致癌“场效应”导致几个癌前克隆，从而引起这些多克隆恶性肿瘤。
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.