Lundberg C, Skoog L, Cavenee W K, Nordenskjöld M
Proc Natl Acad Sci U S A. 1987 Apr;84(8):2372-6. doi: 10.1073/pnas.84.8.2372.
The genotypes at chromosomal loci defined by recombinant DNA probes revealing restriction fragment length polymorphisms were determined in constitutional and tumor tissue from 10 cases of ductal breast cancer: eight premenopausal females and two males. Somatic loss of constitutional heterozygosity was observed at loci on chromosome 13 in primary tumor tissue from three females and one male. In two cases, specific loss of heterozygosity at three distinct genetic loci along the length of the chromosome was observed. In another case, concurrent loss of alleles at loci on chromosomes 2, 13, 14, and 20 was detected, whereas a fourth case showed loss of heterozygosity for chromosomes 5 and 13. In each instance, the data were consistent with loss of one of the homologous chromosomes by mitotic nondisjunction. Analysis of loci on several other chromosomes showed retention of constitutional heterozygosity suggesting the relative specificity of the events. In contrast, similar analyses of other breast cancers, including comedocarcinoma, medullary carcinoma, and juvenile secretory carcinoma, showed no loss of alleles at loci on chromosome 13. These data indicate that the pathogenesis of ductal breast cancer may, in a substantial proportion of cases, involve unmasking of a recessive locus on chromosome 13 and suggest the involvement of such a locus in heritable forms of this disease.
利用揭示限制性片段长度多态性的重组DNA探针，测定了10例导管型乳腺癌（8例绝经前女性和2例男性）的正常组织和肿瘤组织中染色体位点的基因型。在3例女性和1例男性的原发性肿瘤组织中，观察到13号染色体位点上的体细胞性杂合性缺失。在2例中，观察到沿染色体长度的3个不同基因位点的特异性杂合性缺失。在另一例中，检测到2号、13号、14号和20号染色体位点上等位基因的同时缺失，而第4例显示5号和13号染色体的杂合性缺失。在每种情况下，数据均与有丝分裂不分离导致的一条同源染色体缺失一致。对其他几条染色体上的位点分析显示保留了正常杂合性，提示这些事件具有相对特异性。相比之下，对其他乳腺癌（包括粉刺癌、髓样癌和幼年分泌性癌）的类似分析显示，13号染色体位点上没有等位基因缺失。这些数据表明，在相当比例的病例中，导管型乳腺癌的发病机制可能涉及13号染色体上隐性位点的暴露，并提示该位点参与了这种疾病的遗传形式。
