Cool M, Jolicoeur P
Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Quebec, Canada.
Cancer Res. 1999 May 15;59(10):2438-44.
Loss of heterozygosity (LOH) analysis was performed on 62 mammary tumors that were induced in (BALB/c x C57BL/6)F1 mouse mammary tumor virus/neu transgenic mice. Eighty-six simple sequence length polymorphism markers were used to cover all of the somatic chromosomes. Frequency of LOH was observed to be significant for chromosomes 4 (50%), 19 (32%), and 8 (21%). On chromosome 4, at least three distinct regions of allelic deletions could be identified: one proximal to 22 cM; the second close to the p16INK4a/p15INK4b locus, which is commonly deleted in various tumors; and the third one in the proximity of Mom1. The frequency of LOH on chromosome 19 was the same for the four markers used. Our data suggested the presence of two distinct LOH loci, one proximal to 47 cM and the other at the distal region. On chromosome 8, possibly two distinct LOH loci could be recognized, one around 52 cM and the other one at 67 cM or distal to it. These regions map close to E-cadherin (Cdh1) and M-cadherin (Cdh15) loci, respectively. Because LOH sites are thought to harbor tumor suppressor genes, this allelotype screening has allowed the mapping of putative tumor suppressor genes that may be implicated, in collaboration with the erbB-2/neu oncogene, in the development of mammary tumors in these transgenic mice.
对62个在（BALB/c×C57BL/6）F1小鼠乳腺肿瘤病毒/neu转基因小鼠中诱发的乳腺肿瘤进行了杂合性缺失（LOH）分析。使用86个简单序列长度多态性标记覆盖所有体细胞染色体。观察到4号染色体（50%）、19号染色体（32%）和8号染色体（21%）的LOH频率具有显著性。在4号染色体上，可识别出至少三个不同的等位基因缺失区域：一个靠近22 cM；第二个靠近p16INK4a/p15INK4b位点，该位点在各种肿瘤中通常缺失；第三个在Mom1附近。所使用的四个标记在第19号染色体上的LOH频率相同。我们的数据表明存在两个不同的LOH位点，一个靠近47 cM，另一个在远端区域。在8号染色体上，可能识别出两个不同的LOH位点，一个在52 cM左右，另一个在67 cM或其远端。这些区域分别靠近E-钙黏蛋白（Cdh1）和M-钙黏蛋白（Cdh15）位点。由于LOH位点被认为含有肿瘤抑制基因，这种等位基因分型筛选有助于定位可能与erbB-2/neu癌基因协同参与这些转基因小鼠乳腺肿瘤发生的假定肿瘤抑制基因。
