Department of Obstetrics and Gynecology, University of Cologne School of Medicine, Kerpener Str 34, 50931 Cologne, Germany.
Anticancer Res. 2010 Sep;30(9):3445-9.
High frequencies of loss of heterozygosity (LOH) are found in familial breast carcinomas with BRCA mutations. Although LOH of BRCA1 does not coincide with somatic BRCA1 mutations, reduced BRCA1 protein expression and hypermethylation indicate the involvement of BRCA1 in sporadic carcinogenesis. To further investigate the role of BRCA we determined LOH of BRCA1 and correlated this with LOH in other breast cancer-associated regions.
A total of 105 sporadic breast carcinomas were analysed for LOH in the regions of BRCA1, BRCA2, TP53, Caveolin1, "putative BRCA3", PTEN, ATM and E-cadherin and correlated it with clinicopathological features.
We found an overall increase of LOH in carcinomas with simultaneous LOH of BRCA1. Significantly higher LOH rates were detected in the regions of TP53 (80%: 34.7%; p<0.005), 8q21 (72.7%: 30.6%; p<0.010) and 10q22-23 (21.1%: 5.9%; p=0.043). Moreover, estrogen receptor-negative carcinomas revealed LOH of BRCA1 more frequently than estrogen receptor-positive carcinomas (39%: 12%; p=0.003).
These data indicate that LOH of BRCA1 coincides with a defect of the DNA repair pathway. Therefore, LOH of BRCA1 determines a subgroup of sporadic breast carcinomas sharing genotype/phenotype features with familial breast carcinomas.
BRCA 基因突变的家族性乳腺癌高频出现杂合性缺失（LOH）。尽管 BRCA1 的 LOH 并不与体细胞 BRCA1 突变吻合，但 BRCA1 蛋白表达减少和超甲基化表明 BRCA1 参与了散发性癌变。为了进一步研究 BRCA 的作用，我们确定了 BRCA1 的 LOH，并将其与其他乳腺癌相关区域的 LOH 相关联。
对 105 例散发性乳腺癌进行了 BRCA1、BRCA2、TP53、Caveolin1、“假定 BRCA3”、PTEN、ATM 和 E-cadherin 区域的 LOH 分析，并将其与临床病理特征相关联。
我们发现同时存在 BRCA1 LOH 的癌中 LOH 总体增加。在 TP53 区域（80%：34.7%；p<0.005）、8q21 区域（72.7%：30.6%；p<0.010）和 10q22-23 区域（21.1%：5.9%；p=0.043）检测到显著更高的 LOH 率。此外，雌激素受体阴性的癌比雌激素受体阳性的癌更频繁地出现 BRCA1 的 LOH（39%：12%；p=0.003）。
这些数据表明 BRCA1 的 LOH 与 DNA 修复途径的缺陷吻合。因此，BRCA1 的 LOH 决定了散发性乳腺癌的一个亚组，其具有与家族性乳腺癌相似的基因型/表型特征。
