Latil A, Baron J C, Cussenot O, Fournier G, Soussi T, Boccon-Gibod L, Le Duc A, Rouëssé J, Lidereau R
Laboratoire d'Oncogénétique, Centre René Huguenin, St.-Cloud, France.
Genes Chromosomes Cancer. 1994 Oct;11(2):119-25. doi: 10.1002/gcc.2870110208.
Accumulation of mutations in oncogenes and tumor suppressor genes transforms a normal cell into a malignant cell by allowing it to escape from normal control of growth. In prostate tumorigenesis, the current model envisages specific mutations of the TP53 tumor suppressor gene and loss of loci, detected by loss of heterozygosity (LOH), on chromosome arms 8p, 10q, 16q, and 18q. In order to determine if alterations frequently found in other adenocarcinomas (breast, ovarian, gastric, colorectal), including losses of genetic material from chromosome arms 1p, 3p, 7q, 8p, 11p, 17p, 17q, and 18q, are also involved in prostate cancer, we examined 20 localized early-stage prostate tumors. We detected no mutations of the TP53 gene. Allelic losses were found from 7q (33%), 8p (50%), 10q (20%), and 18q (33%). Furthermore, as the first step toward isolating tumor suppressor genes on 18q, we used six polymorphic markers and identified a small common deleted region between the chromosome 18 centromere and the D18S19 locus.
致癌基因和肿瘤抑制基因中的突变积累,通过使正常细胞摆脱正常生长控制,将其转变为恶性细胞。在前列腺癌发生过程中,目前的模型设想TP53肿瘤抑制基因发生特定突变,以及通过杂合性缺失(LOH)检测到8号染色体短臂、10号染色体长臂、16号染色体长臂和18号染色体长臂上的基因座缺失。为了确定在其他腺癌(乳腺癌、卵巢癌、胃癌、结直肠癌)中常见的改变,包括1号染色体短臂、3号染色体短臂、7号染色体长臂、8号染色体短臂、11号染色体短臂、17号染色体短臂、17号染色体长臂和18号染色体长臂上的遗传物质丢失,是否也与前列腺癌有关,我们检查了20例局限性早期前列腺肿瘤。我们未检测到TP53基因的突变。发现7号染色体长臂(33%)、8号染色体短臂(50%)、10号染色体长臂(20%)和18号染色体长臂(33%)存在等位基因缺失。此外,作为在18号染色体长臂上分离肿瘤抑制基因的第一步,我们使用了六个多态性标记,并在18号染色体着丝粒和D18S19基因座之间确定了一个小的常见缺失区域。