Detection and cloning of a common region of loss of heterozygosity at chromosome 1p in breast cancer.

Detection and cloning of a common region of loss of heterozygosity at chromosome 1p in breast cancer.
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DOI:
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发表时间:
1995-04
期刊:
影响因子:
11.2
通讯作者:
Hirokazu Nagai;Massimo Negrini;S. L. Carter;D. R. Gillum;Anne L. Rosenberg;Gordon F. Schwartz;C. Cr
Hirokazu Nagai;Massimo Negrini;S. L. Carter;D. R. Gillum;Anne L. Rosenberg;Gordon F. Schwartz;C. Cr
中科院分区:
医学1区
文献类型:
--
作者:
Hirokazu Nagai;Massimo Negrini;S. L. Carter;D. R. Gillum;Anne L. Rosenberg;Gordon F. Schwartz;C. Cr

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1号染色体的短臂在各种人类恶性肿瘤中经常受到重排的影响。在乳腺癌中观察到遗传改变,主要是缺失,这表明在1p染色体上存在假定的肿瘤抑制基因。为了确定变异位点,利用1p染色体上11个高度多态性的微卫星标记检测杂合性缺失。我们分析了52例乳腺癌,在1p染色体上发现了4个常见的缺失区域。52例信息丰富的患者中有22例(42%)至少有1个受影响位点。杂合性缺失最常见的区域是1p31 (11/39; 28%);其他三个常见缺失区域分别为1p36(10/44; 23%)、1p35-36(5/40; 13%)和1p13(8/39; 21%)。这些数据表明,一个或多个推定的肿瘤抑制基因可能位于染色体1p上。我们已经克隆了酵母人工染色体1p31上的整个感兴趣区域。该酵母人工染色体组可用于该区域的精细定位和候选肿瘤抑制基因的克隆。
The short arm of chromosome 1 is frequently affected by rearrangements in a variety of human malignancies. Genetic alterations, predominantly deletions, which are indicative of the presence of a putative tumor suppressor gene at chromosome 1p, are observed in breast cancer. In order to define the altered locus, eleven highly polymorphic microsatellite markers on chromosome 1p were used to detect loss of heterozygosity. We analyzed 52 cases of breast cancer and found 4 common deleted regions at chromosome 1p. Twenty-two of 52 (42%) informative patients showed at least 1 affected locus. The region most frequently exhibiting loss of heterozygosity was 1p31 (11/39; 28%); the other three common deleted regions were 1p36 (10/44; 23%), 1p35-36 (5/40; 13%), and 1p13 (8/39; 21%). These data suggest that one or more putative tumor suppressor genes may reside on chromosome 1p. We have cloned the entire region of interest at 1p31 in yeast artificial chromosomes. This yeast artificial chromosome contig can be used for fine mapping of the region and cloning of the candidate tumor suppressor gene.