Dreyling M H, Bohlander S K, Adeyanju M O, Olopade O I
Department of Medicine, University of Chicago, Illinois 60637.
Cancer Res. 1995 Mar 1;55(5):984-8.
Deletions of chromosomal band 9p21 have been detected in various tumor types including melanoma, glioma, lung cancer, mesothelioma, and bladder cancer. Recently, the CDKN2 gene (p16INK4A, MTS I, CDK41) has been proposed as a candidate tumor suppressor gene because it is frequently deleted in cell lines derived from multiple tumor types. We performed fluorescence in situ hybridization (FISH) with interphase cells using yeast artificial chromosome clones and a cosmid contig of the CDKN2 region. In 10 cell lines (4 glioma, 2 melanoma, 2 non-small cell lung cancer, 2 bladder cancer) with 9p alterations detected by molecular or cytogenetic analysis, interphase FISH with the CDKN2 cosmid contig detected all 9p deletions previously identified by molecular analysis. Using this probe, FISH analysis of primary glioblastoma tumors revealed homozygous deletions of the CDKN2 region in 6 of 9 tumors (67%) whereas a yeast artificial chromosome probe containing the interferon type I (IFN) gene cluster was deleted in only 4 cases (44%). Thus, it is likely that the CDKN2 region is the target of 9p deletions in gliomas. Interphase FISH will play an important role in defining the clinical significance of 9p deletions in primary tumors because it is especially applicable to clinical samples which may be contaminated by normal cells.
在包括黑色素瘤、神经胶质瘤、肺癌、间皮瘤和膀胱癌在内的多种肿瘤类型中均检测到了染色体9p21带的缺失。最近，CDKN2基因（p16INK4A、MTS I、CDK41）被认为是一种候选肿瘤抑制基因，因为它在源自多种肿瘤类型的细胞系中经常缺失。我们使用酵母人工染色体克隆和CDKN2区域的黏粒重叠群对间期细胞进行了荧光原位杂交（FISH）。在通过分子或细胞遗传学分析检测到9p改变的10个细胞系（4个神经胶质瘤、2个黑色素瘤、2个非小细胞肺癌、2个膀胱癌）中，用CDKN2黏粒重叠群进行的间期FISH检测到了所有先前通过分子分析鉴定出的9p缺失。使用该探针，对原发性胶质母细胞瘤肿瘤进行FISH分析发现，9个肿瘤中有6个（67%）的CDKN2区域存在纯合缺失，而含有I型干扰素（IFN）基因簇的酵母人工染色体探针仅在4例（44%）中缺失。因此，CDKN2区域很可能是神经胶质瘤中9p缺失的靶点。间期FISH将在确定原发性肿瘤中9p缺失的临床意义方面发挥重要作用，因为它特别适用于可能被正常细胞污染的临床样本。
