Schmutzler R K, Fimmers R, Bierhoff E, Lohmar B, Homann A, Speiser P, Kubista E, Jaeger K, Krebs D, Zeillinger R, Wiestler O D, Von Deimling A
Department of Obstetrics and Gynecology, University of Bonn Medical Center, Germany.
Int J Cancer. 1996 Aug 22;69(4):307-11. doi: 10.1002/(SICI)1097-0215(19960822)69:4<307::AID-IJC12>3.0.CO;2-2.
Breast-carcinoma development presumably results from multiple mutational events in tumor-associated genes. Certain results indicate that some tumor-suppressor genes may combine their pathogenetic potential to synergistically promote tumor growth. In an effort to identify such mechanisms in breast tumors, a series of 77 (group I) paired blood tumor samples from patients with sporadic mammary carcinomas was analyzed for loss of heterozygosity with 15 polymorphic markers on the chromosomal arms 7q, 11q, 13q, 16q, 17p and 17q. A significant association was observed for the combination of allelic losses on chromosomes 11q and 16q. In order to confirm these findings, we studied a second independent series of 189 breast-tumor patients (group 2) with comparable histopathological tumor stages. Group 2 was examined for the same genetic alterations using the identical set of polymorphic markers. The data from this group confirmed the detected association of loss of heterozygosity on chromosomes 11q and 16q and indicate the cooperation of putative tumor-suppressor genes on the chromosomal arms 11q and 16q in a sub-set of breast carcinomas. The regions involved harbor the candidate genes ATM (mutated in ataxiatelangiectasia) on chromosome 11q23 and UVO (uvomorulin, cadherin E) and BBCI (breast basic conserved I) on chromosome 16q22-q24.
乳腺癌的发生可能是由肿瘤相关基因中的多个突变事件引起的。某些结果表明，一些肿瘤抑制基因可能会结合它们的致病潜力，协同促进肿瘤生长。为了确定乳腺肿瘤中的此类机制，对来自散发性乳腺癌患者的一系列77对（第一组）血液肿瘤样本进行了分析，以检测7号染色体长臂、11号染色体长臂、13号染色体长臂、16号染色体长臂、17号染色体短臂和17号染色体长臂上15个多态性标记的杂合性缺失情况。观察到11号染色体和16号染色体上等位基因缺失的组合之间存在显著关联。为了证实这些发现，我们研究了第二组独立的189例乳腺肿瘤患者（第二组），这些患者具有相似的组织病理学肿瘤分期。使用相同的多态性标记集对第二组患者进行相同的基因改变检测。该组数据证实了在11号染色体和16号染色体上检测到的杂合性缺失关联，并表明在一部分乳腺癌中，11号染色体长臂和16号染色体长臂上假定的肿瘤抑制基因存在协同作用。所涉及的区域包含位于11号染色体长臂23区的候选基因ATM（在共济失调毛细血管扩张症中发生突变）以及位于16号染色体22区至24区的UVO（桥粒芯糖蛋白、钙黏蛋白E）和BBCI（乳腺基本保守基因I）。
