Development of FISH Molecular Diagnostics to support Clinical Trials at NCI

染色体病理组（CPU）成立于2010年，以满足“内部”实验室FISH测试的需求，以支持NCI的临床试验。FISH诊断将是病理学实验室目前提供的病理学分子诊断的一个组成部分。在最近的CAP报告中发现，FISH诊断的敏感性和特异性接近100%，这使其在其他基于PCR和免疫组织化学的可用测试中处于领先地位，这些测试长期存在已知的特异性问题。该单位配备了国家的最先进的实验室，包括一个新的蔡司荧光显微镜与载脂蛋白组功能，允许FISH分析和成像厚组织切片，SKY-cube光谱核型-一个现代工具，用于检测染色体易位在癌细胞和各种遗传综合征。购买了所有用于测量DNA数量的小型设备，运行PCR以验证FISH数据，以及用于培养细胞的CO2培养箱。开发/验证的测试包括Her-2扩增在乳腺癌患者中，cmyc易位在Burkitt和弥漫性大B细胞淋巴瘤中，1p/19q缺失测试作为脑肿瘤的预后和诊断标记，Bcl-2易位检测在滤泡性淋巴瘤和其他血液系统恶性肿瘤中，Alk-4易位在肺癌、血液系统和儿童癌症中。其他正在进行的测试包括用于检测膀胱癌中改变细胞的Urovision（雅培拉），用于检测肾肿瘤中的TFE-3易位，肺癌中的EML-4易位，儿童肿瘤（尤文氏肉瘤和Rabdomyosarcoma）中的EWSR1和FLI1易位等。该实验室正在接受CAP认证，以便开始接受用于诊断的患者样本。

The Chromosome Pathology Unit (CPU)was set up in 2010 to fulfill the need in the "in house" laboratory FISH tests required to support clinical trials at NCI. FISH diagnostics will be an integral part of the Pathology molecular diagnostics currently offered by the Lab of Pathology. The sensitivity and specificity of FISH diagnostics was found to be near 100% in recent reports of CAP that puts them in front line among other available tests based on PCR and immunohistochemistry that have a long-known specificity problem. The Unit has been equipped as state-of-the art laboratory that includes a new Zeiss epifluorescence microscope with the ApoTome feature that allows FISH analysis and imaging of thick tissue sections, SKY-cube for spectral karyotyping - a modern tool for the detection of chromosomal translocations in cancer cells and various hereditary syndromes. All small equipment to measure the DNA quantity, run PCR to validate the FISH data, the CO2 incubator to grow cells were purchased as well. The developed/ validated tests include Her-2 amplification in Breast Cancer Patients, cmyc translocation in Burkitt, and Diffuse Large B Cell Lymphomas, 1p/19q deletion tests as prognostic and diagnostic markers for brain tumors, Bcl-2 translocation detection in Follicular Lymphoma and other hematological malignancies, Alk-4 translocation in lung, hematological and pediatric cancers. Other tests that are in the pipeline include Urovision (Abbott) for the detection of altered cells in Bladder Cancer, TFE-3 translocation in kidney tumors, EML-4 translocation in lung cancer, EWSR1, FLI1 translocations in pediatric tumors (Ewing's sarcoma and Rabdomyosarcoma), etc. The lab is in the process to undergo CAP certification to start accepting patient samples for diagnostics.