PDF(Pubmed)
Abstract：
The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.
摘要：
在Ramazzini研究所（RI）的SpragueDawley（SD）大鼠中检查了与终生暴露于射频辐射（RFR）相关的癌症危险，意大利。胶质瘤和心脏神经鞘瘤的发病率增加。这些罕见的大鼠肿瘤与人类疾病的翻译相关性知之甚少。我们通过与人类神经胶质增生相关的重要癌症基因的分子表征，检查了RFR衍生的大鼠肿瘤的遗传改变。基于前23个直系同源人神经胶质瘤相关基因，为大鼠设计了靶向下一代测序（NGS）组。在大鼠神经胶质瘤和心脏神经鞘瘤中表征了单核苷酸变体（SNV）和小插入和缺失（indel）。通过与癌症中的体细胞突变目录（COSMIC）数据库进行比较，确定了大鼠肿瘤中这些遗传改变与人类疾病的翻译相关性。这些数据表明，终生暴露于RFR的大鼠神经胶质瘤在组织学上类似于低度人类神经胶质瘤，但令人惊讶的是，在与人类IDH1p.R132或IDH2p.R172具有同源性的大鼠神经胶质瘤中未检测到突变，这表明大鼠神经胶质瘤主要是涉及人类神经胶质瘤的IDH热点突变的野生型。大鼠神经胶质瘤似乎与IDH1野生型人类神经胶质瘤共享一些遗传改变，大鼠心脏神经鞘瘤在某些被查询的癌症基因中也存在突变。这些数据表明,基于肿瘤特异性直向同源人类癌症驱动基因的靶向NGS组是检查由慢性/终身啮齿动物生物测定产生的啮齿动物肿瘤的翻译相关性的重要工具。
