Jacks T
Howard Hughes Medical Institute, Massachusetts Institute of Technology Center for Cancer Research, Cambridge 02139, USA.
Annu Rev Genet. 1996;30:603-36. doi: 10.1146/annurev.genet.30.1.603.
Over the past several years, a number of human tumor suppressor genes have been cloned and characterized. Germline mutations in tumor suppressor genes strongly predispose to cancer, and they are also mutated somatically in sporadic forms of the disease. In order to create animal models for the familial cancer syndromes caused by inherited mutations in these genes as well as to determine their role in embryogenesis, the homologues of several members of this class have been mutated in the mouse. The initial characterization of the heterozygous and homozygous phenotypes caused by these mutations has led to important insights into the mechanisms by which tumor suppressor genes participate in normal development and how their loss contributes to tumorigenesis.
在过去几年中,许多人类肿瘤抑制基因已被克隆和鉴定。肿瘤抑制基因中的种系突变极易引发癌症,并且它们在散发性疾病形式中也会发生体细胞突变。为了创建由这些基因的遗传突变引起的家族性癌症综合征的动物模型,以及确定它们在胚胎发生中的作用,该类别的几个成员的同源物已在小鼠中发生突变。由这些突变引起的杂合子和纯合子表型的初步表征,为肿瘤抑制基因参与正常发育的机制以及它们的缺失如何导致肿瘤发生提供了重要的见解。