MOLECULAR CYTOGENETICS OF SOLID TUMORS

该项目的目标是确定经常性的遗传改变 与肿瘤的发展相关，并提供 癌症的早期检测和预后评估，特别是 in solid实体tumors肿瘤.基因定位是分子生物学的基础 分析癌细胞中的染色体改变。多种生长 已经发现调节基因与癌症特异性 易位或缺失。复发性基因组改变， 潜在的预测或诊断价值被确定在几个 使用荧光的分子细胞遗传学程序在恶性肿瘤中 原位杂交（FISH）。在卡波西肉瘤（KS）缺失和 易位非随机地涉及脆性区域3 p14，和 3 p上基因座的相关杂合性丢失，包括a FHIT基因在两个肿瘤细胞中被鉴定 线这代表了产生分子的第一步。 用于检测KS发展早期肿瘤细胞的探针。 用着丝粒3号染色体探针和YAC探针进行FISH， 3 p14区域目前用于细胞学制备以检测 KS病变中的肿瘤细胞。在过去的几年里， 在宫颈癌组织中，1、3、8、11和17号染色体的阳性率分别为10%和10%， carcinoma.这些变化得到了证实，新的变化， 染色体显带检测不到的，通过荧光鉴定， 原位杂交（FISH）和光谱核型，一种新的方法， 同时多探针杂交和全局可视化 癌细胞的结构重排。用这些染色体进行FISH 现在用于诊断可疑病例的子宫颈抹片检查。人 在黑色素瘤细胞系中，发现足叶乙甙耐药性与 获得了多个拷贝的突变拓扑异构酶II α基因等位基因由于一系列的数字和结构 17号染色体的改变相反， 人白血病细胞与拓扑异构酶I突变有关 20号染色体没有改变。几个新分离的基因 已经在人类染色体中被绘制出来了。人血管内皮 生长因子基因，NAB-2基因，神经生长的辅抑制因子 因子诱导基因和两个Ras交换因子基因已被定位 在染色体6p 12、12 q13 -14、15 q24和2 p21 -22上， 多药耐药基因定位于大鼠染色体4 q14， 在叙利亚仓鼠中分离的第一个癌基因位于X染色体上 染色体涉及这些基因位点的结构改变 现在可以检查。

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.