MOLECULAR CYTOGENETICS OF SOLID TUMORS

实体瘤的分子细胞遗传学

• 批准号: 2463833
• 负责人: N C POPESCU
• 金额: --
• 依托单位: DIVISION OF BASIC 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/2463833
• 关键词: Kaposi's sarcoma; animal genetic material tag; artificial chromosomes; cervix neoplasms; chromosome aberrations; chromosome deletion; chromosome translocation; cytogenetics; early diagnosis; fluorescent in situ hybridization; genetic mapping; genetic markers; hamsters; human genetic material tag; human tissue; karyotype; laboratory rat; loss of heterozygosity; molecular oncology; neoplasm /cancer diagnosis; neoplasm /cancer genetics; nucleic acid probes; prognosis

The objective of project is to identify recurrent genetic alterations that are relevant to the neoplastic development and provide markers for an early detection and prognostic assessment of cancer, particularly in solid tumors. Localization of genes is essential for molecular analysis of chromosomal alterations in cancer cells. A number of growth regulatory genes have been found to be associated with cancer-specific translocations or deletions. Recurrent genomic alterations having potentially predictive or diagnostic value were identified in several malignancies using molecular cytogenetic procedures of fluorescence in situ hybridization (FISH). In Kaposi's sarcoma (KS) deletions and translocations non-randomly involving the region of fragility 3p14, and related loss of heterozygosity of loci on 3p, including the loci of a newly isolated FHIT gene, were identified in two tumorigenic cell lines. This represents a first step toward the generation of molecular probes for detecting neoplastic cells early in the development of KS. FISH with centromeric chromosome 3 probe and a YAC probe spanning the 3p14 region are currently used in cytological preparations to detect neoplastic cells in KS lesions. In the past years nonrandom alterations of chromosomes 1, 3, 8, 11 and 17 were identified in cervical carcinoma. These alterations were confirmed and new changes, undetectable by chromosome banding, were identified by fluorescence in situ hybridization (FISH), and spectral karyotype, a new method for simultaneous multiprobe hybridization and global visualization of structural rearrangements in cancer cells. FISH with these chromosomes are now used for diagnosis on PAP smears in ambiguous cases. In human melanoma cell lines, etoposide resistance was found to be associated with the acquisition of multiple copies of a mutant topoisomerase II alpha gene allele due to a series of numerical and structural alterations of chromosome 17. In contrast, camptothecin resistance of human leukemic cell is associated with topoisomerase I mutation in the absence of alterations of chromosome 20. Several newly isolated gene have been mapped in human chromosomes. Human vascular endothelial growth factor gene, NAB-2 gene a corepressor of the nerve growth factor-induced gene, and two Ras exchange factor genes have been mapped to chromosomes 6p12, 12q13-14, 15q24 and 2p21-22, respectively.Two rat multidrug resistance genes were mapped on rat chromosome 4q14, and the first oncogene isolated in Syrian hamster was localized on X chromosome. Structural alterations involving the loci of these genes can now be examined.

该项目的目标是识别反复发生的基因改变 它们与肿瘤的发展相关，并为 癌症的早期发现和预后评估，特别是 在实体瘤中。基因定位是分子生物学研究的关键 癌细胞中染色体变化的分析。多项增长 已发现调控基因与癌症特异性相关 易位或缺失。反复发生的基因组改变有 在以下几个方面确定了潜在的预测或诊断价值 应用荧光分子细胞遗传学技术治疗恶性肿瘤的研究 原位杂交(FISH)在卡波西肉瘤(KS)中的缺失和 易位非随机涉及脆性区域3p14，以及 3P上基因座的相关杂合性丢失，包括A 新分离的FHIT基因在两个致瘤细胞中被鉴定 台词。这代表着朝着分子的产生迈出了第一步。 在KS发生早期检测肿瘤细胞的探讨 带有着丝粒3号染色体探针的FISH和横跨 3p14区域目前用于细胞学准备，以检测 KS皮损中的肿瘤细胞。在过去的几年里，非随机的变化 1、3、8、11和17号染色体 癌症。这些变化得到了证实，也有了新的变化， 不能通过染色体显带检测到的，通过荧光在 原位杂交(FISH)和光谱核型，一种新的检测方法 同时多探针杂交和全局可视化 癌细胞的结构重排。用这些染色体钓鱼 现在用于不明确病例的PAP涂片诊断。在人类中 黑色素瘤细胞株，依托泊苷耐药被发现与 通过获得突变的拓扑异构酶II的多个拷贝 阿尔法基因等位基因的一系列数值和结构 17号染色体的改变。相比之下，喜树碱耐药 人类白血病细胞与拓扑异构酶I突变相关 20号染色体无变化。几个新分离的基因 已经被绘制在人类染色体上。人血管内皮细胞 生长因子基因、NAB-2基因--神经生长抑制因子 因子诱导基因和两个RAS交换因子基因已被定位 分别位于染色体6p12、12q13-14、15q24和2p21-22。 多药耐药基因被定位在大鼠染色体4Q14上， 在叙利亚仓鼠中分离到的第一个癌基因被定位在X 染色体。涉及这些基因的基因座的结构改变 现在可以进行检查了。