Sugita M, Tanaka N, Davidson S, Sekiya S, Varella-Garcia M, West J, Drabkin H A, Gemmill R M
Division of Medical Oncology, University of Colorado Health Sciences Center, Denver 80262, USA.
Cancer Genet Cytogenet. 2000 Feb;117(1):9-18. doi: 10.1016/s0165-4608(99)00135-1.
A common amplification target encompassing chromosome region 3q25 to q27 has been identified by comparative genomic hybridization analyses in tumors of the cervix, ovary, endometrium, lung, and head and neck. Because this segment spans at least 30 megabases, we undertook a molecular analysis of copy number to more precisely define the amplification domain. Our Southern blot and fluorescence in situ hybridization results with the use of 17 markers confirmed the presence of low-level 3q amplification events in cervical, ovarian, and variant SCLC tumors. Most of the tumor types studied appeared to have similar, broad amplification domains centered within 3q26.2, suggesting that the same target is being affected in all. The ovarian carcinoma cell line NIH:OVCAR3 had a highly restricted amplification domain spanned by four overlapping YAC clones, suggesting a small target. The region of highest amplification included the gene for the RNA component of telomerase (hTR), supporting it as a potential target. Although the importance of low-level amplification is unknown, the consistent and reproducible nature of this event in a variety of carcinomas suggests that 3q26.2 harbors an oncogene whose low-level amplification has a significant influence on tumor biology.
通过比较基因组杂交分析,在子宫颈、卵巢、子宫内膜、肺及头颈部肿瘤中已鉴定出一个包含染色体3q25至q27区域的常见扩增靶点。由于该片段跨度至少为30兆碱基,我们对拷贝数进行了分子分析,以更精确地界定扩增区域。我们使用17个标记进行的Southern印迹和荧光原位杂交结果证实,在子宫颈、卵巢及变异型小细胞肺癌肿瘤中存在低水平的3q扩增事件。大多数所研究的肿瘤类型似乎具有相似的、广泛的扩增区域,以3q26.2为中心,这表明所有肿瘤中的同一靶点均受到影响。卵巢癌细胞系NIH:OVCAR3具有一个高度局限的扩增区域,由四个重叠的酵母人工染色体(YAC)克隆覆盖,提示存在一个小靶点。扩增最高的区域包括端粒酶RNA成分(hTR)的基因,这支持其作为一个潜在靶点。尽管低水平扩增的重要性尚不清楚,但该事件在多种癌中的一致性和可重复性表明,3q26.2含有一个癌基因,其低水平扩增对肿瘤生物学有重大影响。