MOLECULAR CHARACTERIZATION OF SOLID PEDIATRIC TUMORS

“儿科实体肿瘤的准确诊断 需要结合诊断技术，包括反向 转录聚合酶链反应（RT-PCR）。许多儿科 实体瘤表现出基本的细胞遗传学异常， 在其发病机制中有一定的意义。尤文氏肉瘤家族 的肿瘤（ESFT）和腺泡状横纹肌肉瘤（RMS）， 其特征在于一致的染色体易位 导致基因的融合和随后的新基因的形成。 嵌合基因这些分子标记物可以通过 RT-PCR或荧光原位杂交（FISH），并且可以 不仅用于建立诊断困难的情况下，但也 了解这些肿瘤的发病机制。近日 这些融合基因的产物已成为疫苗的靶点 儿科肿瘤学新制定方案中的治疗 NCI的分支（POB）。本项目的目标是：（1） 提供最先进的儿科实体肿瘤诊断（2）， 协助评估儿科肿瘤标本， 存在或不存在特异性融合转录物，以及（3） 评价分子标志物在诊断中的意义， 小儿肉瘤的分类和发病机制。以下 去年取得的成绩：（1）共120项 发布儿科病理学报告。(2)共60个RT-PCR 报告已经发布。(3)一系列的50例儿童肉瘤， 通过RT-PCR和常规方法进行评价。研究 表明在选定的病例中需要RT-PCR进行诊断， 应结合形态学结果进行解释（4） FISH是一种非常有用的检测石蜡中融合产物的技术 （5）嗅神经母细胞瘤EWS/Fli-1阴性 与ESFT相反，通过FISH检测融合转录物。（六） 酪氨酸羟化酶基因座的微卫星标记 11号染色体有助于RMS与其它类型的RMS的鉴别 梭形细胞肉瘤，但不能区分肺泡和 胚胎型横纹肌肉瘤"

"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 120 Pediatric Pathology reports were issued. (2) A total of 60 RT-PCR reports were issued. (3) A series of 50 pediatric sarcomas were evaluated by RT-PCR and conventional methods. The study showed that RT-PCR is needed for diagnosis in selected cases and should be interpreted in conjuction with the morphlogic findings (4) FISH is a very useful technique to detect fusion products in paraffin sections (5) Olfactory neuroblastoma is negative for the EWS/Fli-1 fusion transcripts by FISH, in contrast to the ESFT. (6) Microsatellite markers at the tyrosine hydroxylase locus in chromosome 11p are helpful in the distinction of RMS from other spindle cell sarcomas, but not in the distinction of alveolar from embryonal RMS."