Diagnostic Tools--Chromosome/Genetic Markers of Tumors

诊断工具——肿瘤的染色体/遗传标记

• 批准号: 6558747
• 负责人: Thomas E. Ried
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6558747
• 关键词: aneuploidy; biomedical automation; brca gene; breast neoplasms; carcinogenesis; cervix neoplasms; chromosome aberrations; chromosome translocation; computer program /software; cytogenetics; diagnosis design /evaluation; diagnosis quality /standard; epithelium; fluorescent dye /probe; gene mutation; genetic markers; imaging /visualization /scanning; karyotype; neoplasm /cancer diagnosis; neoplasm /cancer genetics; neoplastic process; nucleic acid probes

CGH analyses of human tumors have revealed that chromosomal aberrations result in genomic imbalances specific for different tumor from diverse tissue types. Furthermore, these changes define discrete steps in the progression of epithelial tumors. More than 90% of cervical carcinomas carry extra copies of chromosome 3 and virtually all diploid breast cancers show a gain of chromosome 1q. Also, gains of chromosome 3q precede copy number increases of chromosomes 5p and 1, and loss of chromosome 2 during the genesis of cervical carcinomas. It is therefore conducive to apply the visualization of these recurring and specific chromosomal aberrations to complement and enhance the cytomorphological diagnosis of human cancers and their precursor lesions. This can be achieved using interphase cytogenetics with fluorescently tagged DNA probes that recognize specific chromosomal target regions directly in interphase cells. We have focused on four applications: - Identification of the progressive potential of cervical intraepithelial neoplasia based on the detection of extra copies of chromosome 3 and 5 in thinprep PAP-smears. - Diagnosis and prognostication of suspicious breast lesions following the detection of chromosomal aneuploidies in fine needle aspirates. - Analysis of cytological preparations from ductal lavage and nipple aspirate samples from BRCA1-mutation carries. - Visualization of specific chromosomal aneuploidies in cytokeratin positive epithelial cells isolated from the peripheral blood of breast cancer patients. These projects are accompanied by the improvement of procedures for the preparation of cytological specimens for interphase cytogenetics, by the development of directly labeled, multicolor probe cocktails for relevant chromosomal regions, oncogenes, and tumor suppressor genes (supported by a CRADA with Vysis, Inc.), and by the development of semi-automated or automated microscope hardware and imaging software for fluorescent spot counting.

人类肿瘤的CGH分析已经揭示了染色体畸变导致基因组不平衡，其特异性针对来自不同组织类型的不同肿瘤。此外，这些变化定义了上皮肿瘤进展中的离散步骤。超过90%的宫颈癌携带3号染色体的额外拷贝，几乎所有二倍体乳腺癌都显示染色体1q的增加。此外，在宫颈癌的发生过程中，染色体3q的获得先于染色体5p和1的拷贝数增加以及2号染色体的丢失。 因此，它是有益的应用这些复发性和特定的染色体畸变的可视化，以补充和加强人类癌症及其前驱病变的细胞形态学诊断。这可以使用间期细胞遗传学与荧光标记的DNA探针，识别特定的染色体靶区域直接在间期细胞。我们专注于四个应用： - 基于薄层PAP涂片中3号和5号染色体额外拷贝的检测来鉴别宫颈上皮内瘤变的进展潜力 - 细针抽吸物染色体非整倍体检测后可疑乳腺病变的诊断和鉴别。 - BRCA1突变携带者的导管灌洗和乳头抽吸样本的细胞学制备分析。 - 从乳腺癌患者外周血中分离的细胞角蛋白阳性上皮细胞中特异性染色体非整倍体的观察。 这些项目伴随着间期细胞遗传学细胞学标本制备程序的改进，通过开发相关染色体区域、癌基因和肿瘤抑制基因的直接标记的双探针混合物（由CRADA与Vysis，Inc.支持），以及通过开发用于荧光点计数的半自动或自动显微镜硬件和成像软件。