Loss of heterozygosity in bilateral breast cancer
Loss of heterozygosity in bilateral breast cancer
复制标题
DOI：
10.1023/a:1026575619155
复制
发表时间：
2000-12-01
影响因子：
3.8
通讯作者：
Brook, JD
中科院分区：
文献类型：
--
作者：
Kollias, J;Man, S;Brook, JD
早期患双侧乳腺癌的女性很可能携带乳腺癌易感基因的种系突变。本研究的目的是检测患有双侧乳腺癌的年轻女性（年龄< 50岁）左右乳腺癌的一致性基因变化，这些基因变化可能表明遗传乳腺癌易感性。应用微卫星标记检测31例绝经前双侧乳腺癌患者左右侧肿瘤的杂合性缺失（LOH）。选择17p （p53）、17q （BRCA1）、13q （BRCA2）、11q（共济失调毛细血管扩张症- atm）和3p （FHIT）候选基因附近或内的标记。对有血液的病例进行BRCA1和BRCA2突变检测。在16/31（54%）的病例中，至少有一种标记物在左、右肿瘤中被证实存在一致性LOH。在左乳腺癌和右乳腺癌中都有等位基因丢失，每次都有相同的等位基因丢失。这可能意味着一个共同的突变事件。4例左、右乳腺癌D17S791 （BRCA1）等位基因一致缺失。在这些有血液的病例中，有两例发现了BRCA1突变。4例在D13S155 （BRCA2）位点显示一致的LOH。在7例D11S1778 （ATM）和4例D3S1300（映射到FHIT基因）中进一步证实了一致性LOH，这表明这些肿瘤抑制基因可能在乳腺癌患者的这一亚组中发挥作用。D17S786没有一致的等位基因丢失，这表明在这类双侧乳腺癌病例中，p53的种系突变不太可能发生。
Women who develop bilateral breast cancer at an early age are likely to harbour germline mutations in breast cancer susceptibility genes. The aim of this study was to test for concordant genetic changes in left and right breast cancer of young women (age < 50) with bilateral breast cancer that may suggest an inherited breast cancer predisposition. Microsatellite markers were used to test for loss of heterozygosity (LOH) in left and right tumours for 31 women with premenopausal bilateral breast cancer. Markers adjacent to or within candidate genes on 17p (p53), 17q (BRCA1), 13q (BRCA2), 11q (Ataxia Telangiectasia-ATM) and 3p (FHIT) were chosen. Mutational testing for BRCA1 and BRCA2 was performed for cases where blood was available. Concordant LOH in both left and right tumours was demonstrated for at least one of the markers tested in 16/31(54%) cases. Where allelic loss was demonstrated for both left and right breast cancer, the same allele was lost on each occasion. This may suggest a common mutational event. Four cases showed concordant loss of alleles in both left and right breast cancer at D17S791 (BRCA1). BRCA1 mutations were identified in two of these cases where blood was available. Four cases showed concordant LOH at D13S155 (BRCA2). Concordant LOH was further demonstrated in seven cases for D11S1778 (ATM) and four cases for D3S1300 (which maps to the FHIT gene), suggesting a possible role for these tumour suppressor genes in this subgroup of breast cancer patients. No concordant allelic loss was demonstrated for D17S786 suggesting that germline mutations in p53 are unlikely in such cases of bilateral breast cancer.