Nagai M A, Medeiros A C, Brentani M M, Brentani R R, Marques L A, Mazoyer S, Mulligan L M
Departamento de Radiologia, Faculdade de Medicina, Universidade de São Paulo, Brazil.
Oncology. 1995 Nov-Dec;52(6):448-53. doi: 10.1159/000227509.
In this study, we analyzed 105 paired sporadic primary breast tumor and normal tissue samples for loss of heterozygosity (LOH) on chromosome 17, using 12 polymorphic markers. We have identified partial or interstitial LOH in five separate regions of chromosome 17. Two of the deleted regions lie on the short arm of the chromosome, the first (region I, D17S5) in the telomeric part, distal to TP53 and the second spanning the TP53 gene (region II). Three of the five deleted regions lie on the long arm of chromosome 17: region III, on the proximal long arm between D17S250 and THRA1; region IV, between D17S776 and D17S579, including the BRCA1 gene, and region V, located distal to D17S733. No statistically significant correlations were observed between clinicopathological characteristics or steroid hormone receptor status and deletion of either region I or II. However, patients whose tumors had LOH for region I showed relapse or death more frequently than patients with tumors informative for this region but without LOH (p = 0.002). Statistically significant correlations between LOH at each of the three deleted regions of 17q and a high mitotic index were observed (region III, p = 0.005; region IV, p = 0.02, and region V, p = 0.004). In addition, LOH at region IV showed a significant association with paucity of estrogen receptors (p = 0.01). Our results show a complex pattern of LOH on chromosome 17 in breast cancer and a correlation of these events with different clinical parameters. This pattern suggests that particular subsets of allele loss may contribute specifically to different clinically defined subsets of sporadic breast tumors.
在本研究中，我们使用12个多态性标记，分析了105对散发的原发性乳腺肿瘤和正常组织样本中17号染色体上的杂合性缺失（LOH）情况。我们在17号染色体的五个不同区域发现了部分或间质性LOH。其中两个缺失区域位于染色体短臂上，第一个（区域I，D17S5）在端粒部分，位于TP53远端，第二个跨越TP53基因（区域II）。五个缺失区域中的三个位于17号染色体长臂上：区域III，位于D17S250和THRA1之间的近端长臂；区域IV，位于D17S776和D17S579之间，包括BRCA1基因；区域V，位于D17S733远端。在临床病理特征或类固醇激素受体状态与区域I或II的缺失之间未观察到统计学上的显著相关性。然而，肿瘤在区域I发生LOH的患者比该区域有信息但无LOH的肿瘤患者更频繁地出现复发或死亡（p = 0.002）。观察到17q的三个缺失区域中每个区域的LOH与高有丝分裂指数之间存在统计学上的显著相关性（区域III，p = 0.005；区域IV，p = 0.02，区域V，p = 0.004）。此外，区域IV的LOH与雌激素受体缺乏显著相关（p = 0.01）。我们的结果显示了乳腺癌中17号染色体上复杂的LOH模式，以及这些事件与不同临床参数的相关性。这种模式表明特定的等位基因缺失子集可能对散发性乳腺肿瘤的不同临床定义子集有特定贡献。
