Hino O, Klein-Szanto A J, Freed J J, Testa J R, Brown D Q, Vilensky M, Yeung R S, Tartof K D, Knudson A G
Fox Chase Cancer Center, Philadelphia, PA 19111.
Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):327-31. doi: 10.1073/pnas.90.1.327.
Hereditary renal carcinoma (RC) in the rat, originally reported by R. Eker in 1954, is an example of a Mendelian dominant predisposition to a specific cancer in an experimental animal. At the histologic level, RCs develop through multiple stages from early preneoplastic lesions (e.g., atypical tubules) to adenomas in virtually all heterozygotes by the age of 1 year. The homozygous mutant condition is lethal at approximately 10 days of fetal life. Ionizing radiation induces additional tumors in a linear dose-response relationship, suggesting that in heterozygotes two events (one inherited, one somatic) are necessary to produce tumors, and that the predisposing gene is a tumor suppressor gene. No genetic linkage has yet been found between the Eker mutation and rat DNA sequences homologous to those in human chromosome 3p, the presumed site of the putative tumor suppressor gene responsible for human RC. Nonrandom loss of rat chromosome 5 in RC-derived cell lines is sometimes associated with homozygous deletion of the interferon gene loci at rat chromosome bands 5q31-q33. Since this locus is not linked with the predisposing inherited gene in the Eker rat, it probably represents a second tumor suppressor gene involved in tumor progression.
大鼠遗传性肾癌（RC）最初由R.埃克于1954年报道，是实验动物中孟德尔显性遗传易患特定癌症的一个例子。在组织学水平上，几乎所有杂合子在1岁时，RC会从早期癌前病变（如非典型肾小管）经过多个阶段发展为腺瘤。纯合突变状态在胎儿期约10天时致死。电离辐射以线性剂量反应关系诱导额外的肿瘤，这表明在杂合子中，产生肿瘤需要两个事件（一个遗传，一个体细胞事件），并且易感基因是一种肿瘤抑制基因。尚未在埃克突变与与人类3号染色体p臂上序列同源的大鼠DNA序列之间发现遗传连锁，人类3号染色体p臂被认为是负责人类RC的假定肿瘤抑制基因的位点。RC衍生细胞系中大鼠5号染色体的非随机丢失有时与大鼠染色体5q31 - q33带处干扰素基因位点的纯合缺失有关。由于该位点与埃克大鼠中的易感遗传基因不连锁，它可能代表参与肿瘤进展的第二个肿瘤抑制基因。
