Linardic Corinne M
Department of Pediatrics and Pharmacology, Duke University Medical Center, Durham, NC 27710, USA.
Cancer Lett. 2008 Oct 18;270(1):10-8. doi: 10.1016/j.canlet.2008.03.035. Epub 2008 May 23.
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence. The predominant histologic variants of this disease are termed embryonal (eRMS) and alveolar (aRMS), based on their appearance under light microscopy. Of the two, aRMS is associated with an more aggressive disease pattern and a higher mortality, mandating a better understanding of this cancer at the molecular level. The PAX3-FOXO1 fusion gene, resulting from the stable reciprocal translocation of chromosomes 2 and 13, is a signature genetic change found only in aRMS, and thought to be responsible at least in part for its malignant phenotype. This review will discuss the clinical significance of the PAX3-FOXO1 fusion gene, the pertinent historical and current models used to study its oncogenic contributions, the transcriptional targets that are thought to mediate these contributions, and the cellular mechanisms impacted by PAX3-FOXO1 that ultimately lead to aRMS.
横纹肌肉瘤(RMS)是儿童和青少年时期最常见的软组织肉瘤。根据其在光学显微镜下的外观,这种疾病的主要组织学变体被称为胚胎型(eRMS)和肺泡型(aRMS)。在这两种类型中,aRMS与更具侵袭性的疾病模式和更高的死亡率相关,这就需要在分子水平上更好地了解这种癌症。PAX3-FOXO1融合基因由2号和13号染色体的稳定相互易位产生,是仅在aRMS中发现的标志性基因变化,并且被认为至少部分地导致了其恶性表型。本综述将讨论PAX3-FOXO1融合基因的临床意义、用于研究其致癌作用的相关历史和当前模型、被认为介导这些作用的转录靶点,以及受PAX3-FOXO1影响最终导致aRMS的细胞机制。