Takeuchi S, Mori N, Koike M, Slater J, Park S, Miller C W, Miyoshi I, Koeffler H P
Division of Hematology/Oncology, Cedars-Sinai Research Institute, University of California, Los Angeles School of Medicine 90048, USA.
Cancer Res. 1996 Feb 15;56(4):738-40.
To refine the chromosomal localization of a putative tumor suppressor gene, we analyzed the loss of heterozygosity (LOH) of chromosome 12 in 36 primary non-small cell lung cancer (NSCLC) samples with matched normal DNA using 22 highly informative polymorphic markers. Twelve cases showed LOH at one or more loci on chromosome 12. LOH of chromosome arm 12p was more frequent in large cell carcinoma than squamous cell carcinoma, indicating molecular genetic heterozygosity within the major NSCLC subtypes. We identified the smallest commonly deleted region on chromosome 12p13. This region is flanked by D12S269 and D12S308, including the KIP1 gene. Mutational analysis of KIP1 using PCR-single strand conformation polymorphism and Southern Blot analysis showed no homozygous deletions, rearrangements, or point mutations, suggesting that the altered gene in this region is not the KIP1 gene. These data suggest that a new tumor suppressor gene which is involved in tumorigenesis of NSCLC is in the region of KIP1.
为了精确定位一个假定的肿瘤抑制基因在染色体上的位置，我们使用22个信息丰富的多态性标记，分析了36例原发性非小细胞肺癌（NSCLC）样本及其匹配的正常DNA中12号染色体的杂合性缺失（LOH）情况。12例样本在12号染色体的一个或多个位点显示出LOH。12p染色体臂的LOH在大细胞癌中比在鳞状细胞癌中更常见，这表明主要NSCLC亚型内存在分子遗传杂合性。我们确定了12p13染色体上最小的常见缺失区域。该区域位于D12S269和D12S308之间，包括KIP1基因。使用PCR-单链构象多态性和Southern印迹分析对KIP1进行突变分析，结果显示没有纯合缺失、重排或点突变，这表明该区域中发生改变的基因不是KIP1基因。这些数据表明，一个参与NSCLC肿瘤发生的新肿瘤抑制基因位于KIP1区域。
