Todd S, Franklin W A, Varella-Garcia M, Kennedy T, Hilliker C E, Hahner L, Anderson M, Wiest J S, Drabkin H A, Gemmill R M
Division of Oncology, University of Colorado Health Sciences Center, Denver 80262, USA.
Cancer Res. 1997 Apr 1;57(7):1344-52.
Cytogenetic and loss of heterozygosity (LOH) studies have demonstrated that deletions of chromosome 3p occur at a high frequency in all forms of lung cancer. To clarify the role of 3p in lung tumorigenesis and to more precisely identify targets for positional cloning efforts, we have performed 3p deletion analyses (microsatellite and fluorescence in situ hybridization) in a series of lung cancer cell lines and uncultured tumor samples. Importantly, we identified homozygous deletions in four uncultured tumors and one cell line. Homozygous deletions were found in three squamous tumors within a region of 3p21 which had previously been described only in cell lines, a 1-2-megabase homozygous deletion in a small cell tumor at 3p12, and a 3p14.2 homozygous deletion in a non-small cell lung carcinoma cell line. The detection of homozygous deletions affecting these multiple regions in uncultured tumor cells substantiates the belief (previously based on deletions found only in tumor cell lines) that these sites contain important tumor suppressor genes. Along with previously reported homozygous deletions in a distal portion of 3p21.3, we now have evidence for four separate regions of 3p which undergo homozygous deletions in either uncultured lung tumors or cell lines.
细胞遗传学和杂合性缺失(LOH)研究表明,3号染色体短臂(3p)缺失在所有类型的肺癌中均高频发生。为阐明3p在肺癌发生中的作用,并更精确地确定定位克隆研究的靶点,我们对一系列肺癌细胞系和未经培养的肿瘤样本进行了3p缺失分析(微卫星分析和荧光原位杂交)。重要的是,我们在4个未经培养的肿瘤和1个细胞系中发现了纯合缺失。在3p21区域的3个鳞状细胞癌肿瘤中发现了纯合缺失,该区域此前仅在细胞系中被描述过;在一个小细胞癌肿瘤的3p12处发现了一个1 - 2兆碱基的纯合缺失;在一个非小细胞肺癌细胞系中发现了3p14.2纯合缺失。在未经培养的肿瘤细胞中检测到影响这些多个区域的纯合缺失,证实了如下观点(此前仅基于在肿瘤细胞系中发现的缺失),即这些位点含有重要的肿瘤抑制基因。连同此前报道的3p21.3远端部分的纯合缺失,我们现在有证据表明,在未经培养的肺癌肿瘤或细胞系中,3p有4个独立区域会发生纯合缺失。