GENETIC ANALYSIS OF HUMAN CELLULAR GENES IN NEOPLASTIC TRANSFORMATION

细胞遗传学、分子生物学、连锁的累积技术 分析和原位杂交导致了鉴定和 超过1500个人类基因座的特征，这个值现在超过了 在果蝇中定位的基因数量。我们将我们的努力集中在 体细胞杂交板与相关基因的原位杂交 肿瘤过程包括(1)细胞原癌基因，(2)生长 因子，(3)生长因子和受体，(4)内源性逆转录病毒 家族，(5)逆转录病毒的整合位点，和(6)限制基因 这界定了逆转录病毒在哺乳动物中的复制。在过去几年里， 人类基因图谱经历了数量的大幅增加 已被映射到特定染色体位置的肿瘤基因座。的 到目前为止，已被染色体定位的35个特定人类基因座，13个 (40%)由遗传科科学家和他们的 合作者。今年我们集中精力了解基因组 几个基因的组织：Rel、Ets、trk、TPR、FMS、Met和内源 逆转录病毒家族。其中三个基因，Ets，Met-Tpr和trk，是 发现是由染色体融合而来的复合基因 不同的功能基因座。这些细胞基因在一个变种中的截断 在人类肿瘤以及某些非肿瘤病理中 (例如，唐氏综合征中的ETS-2或囊性纤维化中的MET) 由它们的染色体位置所暗示的，正在调查中。这个 新出现的基因图谱肿瘤相关基因座继续提供 引发分子遗传学分析的前所未有的机遇 和肿瘤过程的进展。

The cumulative techniques of cell genetics, molecular biology, linkage analysis and in situ hybridization has resulted in the identification and characterization of over 1500 human loci, a value which now exceeds the number of genes mapped in Drosophila. We have concentrated our efforts on somatic cell hybrid panels and in situ hybridizations to genes related to neoplastic processes including (1) cellular proto-oncogenes, (2) growth factors, (3) growth factors and receptors, (4) endogenous retroviral families, (5) integration sites for retrovirus, and (6) restriction genes that delimit retrovirus replication in mammals. Within the last few years, the human gene map has experienced a large increase in the number of neoplasia loci that have been mapped to specific chromosomal positions. Of the 35 specific human loci that have been chromosomally mapped to date, 13 (40%) have been assigned by the Genetics Section scientists and their collaborators. This year we have concentrated on understanding the genomic organization of several genes: rel, ets, trk, tpr, fms, met and endogenous retroviral families. Three of these genes, ets, met-tpr and trk, were found to be composite genes derived from the fusion of chromosomally disparate functional loci. Truncation of these cellular genes in a variety of human neoplasias, as well as in certain non-neoplastic pathologies (e.g., ets-2 in Down's syndrome or met in cystic fibrosis) which were suggested by their chromosomal position, are under investigation. The emerging gene map neoplasia-associated loci continues to provide an unprecedented opportunity for molecular genetic analysis of the initiation and progression of neoplastic processes.