Jain Shilpa, Xu Ruliang, Prieto Victor G, Lee Peng
Department of Pathology, New York University School of Medicine, New York, NY, USA.
Int J Clin Exp Pathol. 2010 Apr 23;3(4):416-28.
Sarcomas are a heterogeneous group of tumors that are traditionally classified according to the morphology and type of tissue that they resemble, such as rhabdomyosarcoma, which resembles skeletal muscle. However, the cell of origin is unclear in numerous sarcomas. Molecular genetics analyses have not only assisted in understanding the molecular mechanism in sarcoma pathogenesis but also demonstrated new relationships within different types of sarcomas leading to a more proper classification of sarcomas. Molecular classification based on the genetic alteration divides sarcomas into two main categories: (i) sarcomas with specific genetic alterations; which can further be subclassified based on a) reciprocal translocations resulting in oncogenic fusion transcripts (e.g. EWSR1-FLI1 in Ewing sarcoma) and b) specific oncogenic mutations (e.g. KIT and PDGFRA mutations in gastrointestinal stromal tumors) and (ii) sarcomas displaying multiple, complex karyotypic abnormalities with no specific pattern, including leiomyo-sarcoma, and pleomorphic liposarcoma. These specific genetic alterations are an important adjunct to standard morphological and immunohistochemical diagnoses, and in some cases have a prognostic value, e. g., Ewing family tumors, synovial sarcoma, and alveolar rhabdomyosarcoma. In addition, these studies may also serve as markers to detect minimal residual disease and can aid in staging or monitor the efficacy of therapy. Furthermore, sarcoma-specific fusion genes and other emerging molecular events may also represent potential targets for novel therapeutic approaches such as Gleevec for dermatofibrosarcoma protuberans. Therefore, increased understanding of the molecular biology of sarcomas is leading towards development of newer and more effective treatment regimens. The review focuses on recent advances in molecular genetic alterations having an impact on diagnostics, prognostication and clinical management of selected sarcomas.
肉瘤是一组异质性肿瘤，传统上根据其相似的组织形态和类型进行分类，例如横纹肌肉瘤，它类似于骨骼肌。然而，许多肉瘤的起源细胞尚不清楚。分子遗传学分析不仅有助于理解肉瘤发病机制中的分子机制，还揭示了不同类型肉瘤之间的新关系，从而使肉瘤的分类更加合理。基于基因改变的分子分类将肉瘤分为两大类：（i）具有特定基因改变的肉瘤；可进一步根据以下情况进行亚分类：a）导致致癌融合转录本的相互易位（例如尤因肉瘤中的EWSR1-FLI1）和b）特定的致癌突变（例如胃肠道间质瘤中的KIT和PDGFRA突变）；以及（ii）显示多种复杂核型异常且无特定模式的肉瘤，包括平滑肌肉瘤和多形性脂肪肉瘤。这些特定的基因改变是标准形态学和免疫组化诊断的重要辅助手段，在某些情况下具有预后价值，例如尤因家族肿瘤、滑膜肉瘤和肺泡横纹肌肉瘤。此外，这些研究还可作为检测微小残留病的标志物，有助于分期或监测治疗效果。此外，肉瘤特异性融合基因和其他新出现的分子事件也可能代表新治疗方法的潜在靶点，例如用于隆突性皮肤纤维肉瘤的格列卫。因此，对肉瘤分子生物学的深入了解正推动着更新、更有效的治疗方案的发展。本综述重点关注对特定肉瘤的诊断、预后和临床管理有影响的分子遗传改变的最新进展。
