Blount P L, Galipeau P C, Sanchez C A, Neshat K, Levine D S, Yin J, Suzuki H, Abraham J M, Meltzer S J, Reid B J
Department of Medicine, University of Washington, Seattle 98195.
Cancer Res. 1994 May 1;54(9):2292-5.
Inactivation of the p53 gene, located on chromosome 17p, leads to genetic instability and aneuploidy in vitro. Aneuploid cell populations from Barrett's adenocarcinomas have a high prevalence of 17p allelic losses, and there is substantial evidence that the target of these losses is the p53 gene. If 17p allelic losses lead to aneuploidy in Barrett's esophagus, then they should be present in diploid cells from patients who develop aneuploidy. We detected 17p allelic losses in diploid cells from 10 of 11 patients (91%) with Barrett's esophagus who developed aneuploid cell populations. Our data strongly suggest that 17p allelic losses precede the development of aneuploidy during neoplastic progression in Barrett's esophagus in vivo and, therefore, support in vitro evidence for the role of p53 in genetic instability.
位于17号染色体短臂上的p53基因失活会导致体外遗传不稳定和非整倍体形成。巴雷特腺癌的非整倍体细胞群体中17号染色体短臂等位基因缺失的发生率很高,并且有大量证据表明这些缺失的靶点是p53基因。如果17号染色体短臂等位基因缺失导致巴雷特食管出现非整倍体,那么它们应该存在于发展为非整倍体细胞群体的患者的二倍体细胞中。我们在11例发展为非整倍体细胞群体的巴雷特食管患者中的10例(91%)的二倍体细胞中检测到了17号染色体短臂等位基因缺失。我们的数据强烈表明,在体内巴雷特食管肿瘤进展过程中,17号染色体短臂等位基因缺失先于非整倍体的形成,因此支持了p53在遗传不稳定中作用的体外证据。