Histologic and Molecular Characterization of Solid Pediatric Tumors

儿科实体肿瘤的准确诊断需要多种诊断技术的结合，包括逆转录聚合酶链反应（RT-PCR）。许多儿童实体瘤表现出基本的细胞遗传学异常，这与其发病机制有关。尤文氏肉瘤家族肿瘤（ESFT）和腺泡状横纹肌肉瘤（RMS）的特征在于一致的染色体易位，其导致基因融合和随后形成新的嵌合基因。这些分子标志物可以通过RT-PCR或荧光原位杂交（FISH）检测，不仅可以用于建立疑难病例的诊断，而且可以了解这些肿瘤的发病机制。最近，这些融合基因的产物已经成为NCI儿科肿瘤学分支（POB）新建立的方案中的疫苗疗法的靶标。本项目的目的是：（1）提供儿科实体肿瘤的最新诊断技术（2）协助评估儿科肿瘤标本中是否存在特异性融合转录本 （3）探讨分子标志物在儿童肉瘤诊断、分型及发病机制中的意义。在过去一年中，取得了以下成绩：（1）共发出122份病理报告。(2)共发布了51份RT-PCR报告。(3)通过RT-PCR评估一系列72例小儿肉瘤中融合转录物的存在或不存在（Dagher，R.等Int J Pediatr Hematol Oncol（出版中））。(4)在评估119例儿科肿瘤病例后，肌细胞生成素被确定为横纹肌肉瘤特异性标志物（Kumar，S等Mod Pathol 2000; 13：988-993）。

Accurate diagnosis of solid pediatric tumors requires a combination of diagnostic techniques including reverse transcription polymerase chain reaction (RT-PCR). Many pediatric solid tumors exhibit fundamental cytogenetic abnormalities that have implications in their pathogenesis. The Ewing's sarcoma family of tumors (ESFT) and alveolar rhabdomyosarcoma (RMS) are characterized by consistent chromosomal translocations which result in the fusion of genes and subsequent formation of novel chimeric genes. These molecular markers can be detected by RT-PCR or fluorescence in situ hybridization (FISH) and can be used not only to establish the diagnosis in difficult cases, but also to understand the pathogenesis of these tumors. Recently, the products of these fusion genes have become the target of vaccine therapies in newly established protocols in the Pediatric Oncology Branch (POB) at the NCI. The objective of this project is: (1) to provide state of the art diagnosis of solid pediatric tumors (2) to assist in the evaluation of pediatric tumor specimens for the presence or absence of specific fusion transcripts and (3) to evaluate the significance of molecular markers in the diagnosis, classification and pathogenesis of pediatric sarcomas. The following accomplishments have been made in the last year: (1) A total of 122 Pathology reports were issued. (2) A total of 51 RT-PCR reports were issued. (3) A series of 72 pediatric sarcomas were evaluated by RT-PCR for the presence or absence of fusion transcripts (Dagher, R. et al Int J Pediatr Hematol Oncol (in press)).(4) Myogenin was established as a rhabdomyosarcoma-specific marker, after evaluation of 119 pediatric tumor cases ( Kumar, S et al. Mod Pathol 2000; 13:988-993).