Tomlinson I P, Strickland J E, Lee A S, Bromley L, Evans M F, Morton J, McGee J O
Nuffield Department of Pathology and Bacteriology, University of Oxford, John Radcliffe Hospital.
J Clin Pathol. 1995 May;48(5):424-8. doi: 10.1136/jcp.48.5.424.
Chromosome 11q23 seems to be a site of frequent mutation in cancer. It also contains loci such as ataxia telangiectasia with possible importance in the pathogenesis of breast tumours. The short arm of chromosome 11 has been studied extensively in breast cancer, but the long arm, in particular the distal part, has been studied less frequently. Cytogenetic analysis has shown possible involvement of chromosome 11q in breast tumours. Chromosome transfer experiments have also implicated chromosome 11q in breast cancer. A high frequency of mutations might therefore be expected to occur on chromosome 11q in breast cancers.
Using restriction fragment analysis, the primary tumours of 41 patients with breast cancer were screened for mutations at five loci on chromosome 11q (D11Z1, INT2, (FGF3), DRD2, NCAM, and D11S29).
Allelic loss occurred at a high frequency (59%) at D11S29. At NCAM, novel alleles were frequently seen on autoradiographs. Relatively low frequencies of mutation were detected at the other loci. Allelic loss at D11S29 was associated with the presence of lymph node metastases, but this may be a chance association.
The frequency of allelic loss at the DS11S29 locus is high. The significance of novel alleles at NCAM and their relation to allelic loss at D11S29 are unclear. The results presented here do not permit fine mapping of a region of allelic loss, but suggest that the region of greatest loss lies distal to DRD2. The results provide further evidence for the importance of gene(s) near 11q23 in the pathogenesis of breast cancer, and of tumours in general.
11号染色体长臂2区3带（11q23）似乎是癌症中频繁发生突变的位点。它还包含诸如共济失调毛细血管扩张症等基因座，这些基因座在乳腺肿瘤的发病机制中可能具有重要意义。11号染色体短臂在乳腺癌中已得到广泛研究，但长臂，尤其是远端部分，研究相对较少。细胞遗传学分析表明11q染色体可能参与乳腺肿瘤的发生。染色体转移实验也表明11q染色体与乳腺癌有关。因此，预计乳腺癌中11q染色体上会出现高频突变。
采用限制性片段分析，对41例乳腺癌患者的原发性肿瘤进行筛查，检测11q染色体上5个基因座（D11Z1、INT2、（FGF3）、DRD2、NCAM和D11S29）的突变情况。
D11S29基因座的等位基因缺失频率较高（59%）。在NCAM基因座，放射自显影片上经常可见新的等位基因。在其他基因座检测到的突变频率相对较低。D11S29基因座的等位基因缺失与淋巴结转移的存在有关，但这可能是一种偶然关联。
DS11S29基因座的等位基因缺失频率较高。NCAM基因座上新等位基因的意义及其与D11S29基因座等位基因缺失的关系尚不清楚。本文给出的结果不允许对等位基因缺失区域进行精细定位，但表明最大缺失区域位于DRD2基因座的远端。这些结果进一步证明了11q23附近基因在乳腺癌及一般肿瘤发病机制中的重要性。
