MOLECULAR CYTOGENETICS OF SOLID TUMORS

这个项目的目标是识别复发的遗传 与肿瘤发展相关的改变，并提供 癌症早期检测和预后评估的标记物， 尤其是在实体瘤中。基因的本地化对于 癌细胞染色体改变的分子分析 特定病源地的识别。1996年7月，一个新的 LEC成立了分子细胞遗传学研究室。这项研究 这一部分的计划主要集中在人和诱导的肝脏 老鼠患上癌症。某些基因组区域表现出更高的脆弱性 以及由于结构染色质组织而导致的重组倾向 和DNA复制--3号染色体短臂的脆弱部位 (FRA3B)经常与缺失、易位和 病毒在几种形式的癌症中整合。FRA3B包含 多发性肿瘤--脆性组氨酸三联体基因的基因座 抑癌基因在多种常见肿瘤中异常表达 各种形式的癌症。通过鱼，使用覆盖地球上特定区域的宇宙 FHIT基因，研究发现，大部分蚜虫素诱导的缺口在 FRA3b属于FHIT基因。这些结果表明， 癌症特异性缺失，通常涉及 FHIT基因起源于FRA3B的断裂。此外，序列还包括 在人类癌症的关键部位容易损伤和重组 都是在基因内水平上鉴定的。角质形成细胞生长因子 胰岛素样生长因子(KGF)是成纤维细胞生长因子家族成员。部分内容 编码KGF的基因是在灵长类动物进化过程中扩增出来的 存在于人类基因组中的多个未经处理的副本中。KGF 在人类和类人猿中鉴定和绘制了序列图，为 对开始的放大和扩散事件的年代测定的洞察 在长臂猿。最重要的是，有证据表明 人与黑猩猩的关系及其可能的选择压力 在高等灵长类动物进化过程中的这种分散 如果是这样的话。几种新分离的肿瘤相关基因的定位 卷曲相关蛋白、忍者蛋白、小鼠细胞周期蛋白G1和 二肽基I型多肽酶基因与三种胶质细胞源性神经营养因子 因子基因具有特殊的重要性，因为它将促进 不明原因遗传病定位中的基因座识别 在相同的染色体区域。

The objective of this project is the identification of 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 and for the identification of specific disease loci. In July 1996 a new Molecular Cytogenetics Section was established in LEC. The research program of this Section focused primarily on human and induced hepatic cancer in mice. Certain genomic regions exhibit an increase fragility and tendency to recombination due to structural chromatin organization and DNA replication A fragile site of the short arm of chromosome 3 (FRA3B) is frequently associated with deletions, translocations and virus integration in several forms of cancer. FRA3B encompasses the locus of the fragile histidine triad (FHIT) gene, a multiple tumor suppressor gene which is abnormally expressed in a variety of common forms of cancer. By FISH, using cosmids covering specific regions of the FHIT gene, it was found that most of the aphidicolin-induced gaps at FRA3B fall within the FHIT gene. These results demonstrate that the cancer-specific deletions, which frequently involve introns 4 and 5 of the FHIT gene, originated through breaks in FRA3B. Also, sequences that are prone to damage and recombination at a critical site in human cancer were identified at the intragenic level. Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor family. Portions of the gene encoding KGF were amplified during primate evolution and are present in multiple non-processed copies in the human genome. KGF sequences were identified and mapped in human and great apes providing insights in the dating of amplification and dispersion events that began in gibbon. Most importantly, evidence for a closer evolutionary relationship of human and chimpanzee and a possible selective pressure for such dispersion during the evolution of higher primates were provided. The localization of several newly isolated cancer-related genes for frizzled-related protein, ninjurin, mouse cyclin G1 and dipeptidyl I peptidase genes, and three glial-derived neurotrophic factor genes is of special importance as it will facilitate the identification of loci in genetic diseases of unknown etiology mapping at the same chromosomal regions.