Histologic and Molecular Characterization of Solid Pediatric Tumors

儿童实体肿瘤的准确诊断需要包括逆转录聚合酶链式反应(RT-PCR)在内的多种诊断技术的结合。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。尤文肉瘤家族肿瘤(ESFT)和肺泡型横纹肌肉瘤(RMS)的特点是一致的染色体易位，导致基因融合和随后形成新的嵌合基因。这些分子标记可通过RT-PCR或荧光原位杂交(FISH)进行检测，不仅可用于疑难病例的诊断，还可用于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儿科肿瘤科(POB)新建立的方案中疫苗治疗的目标。本项目的目标是：(1)提供最先进的儿童实体肿瘤诊断；(2)协助评估儿童肿瘤标本中是否存在特定的融合转录本；(3)评估分子标记在儿童肉瘤的诊断、分类和发病机制中的意义。在过去的一年里，取得了以下成就：(1)共发布了122份病理报告。(2)共发布了51份RT-PCR报告。(3)用RT-PCR法检测了72例儿童肉瘤中是否存在融合转录本(Dagher，R.等人的Int J Pediatr hematol Onol(出版中))。(4)在对119例儿童肿瘤患者(Kumar，S等)进行评估后，确定了肌肉生成素作为横纹肌肉瘤的特异性标记物。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).