Watanabe T, Imoto I, Kosugi Y, Ishiwata I, Inoue S, Takayama M, Sato A, Inazawa J
Department of Molecular Cytogenetics, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Gynecol Oncol. 2001 May;81(2):172-7. doi: 10.1006/gyno.2001.6132.
Little is known about the molecular mechanisms involved in the pathogenesis and/or progression of ovarian cancer (OC). To investigate the genomic imbalances and identify the cancer-related genes associated with this tumor, we applied comparative genomic hybridization (CGH) in OC cell lines.
Chromosomal aberrations among 17 OC cell lines were analyzed with CGH. Since novel chromosomal regions, including 17q21-23, were identified, we examined the involvement of two candidate genes, PS6K and ZNF147, mapped on this chromosomal region. We examined the status of amplification and expression by fluorescence in situ hybridization as well as by Southern blot analysis and by Northern blot analysis on two candidate genes, respectively.
All lines displayed numerous chromosomal imbalances; the most frequent losses were observed on 18q22-23 (29.4%), 13q22-34 (23.5%), 9p (17.6%), 4p11-14 (17.6%), and 11p14-15 (17.6%). The most common gains were noted at 20q12-13 (47.1%), 8q23-24 (35.2%), 5p15 (23.5%), 7q32-36 (23.5%), and 20p (23.5%). High-level gains (HLGs) were detected at 20q12-13 (four cell lines), 8q24 (two cell lines), 12p11-12 (two cell lines), and 17q21-23 (two cell lines). PS6K and ZNF147 genes were amplified in two cell lines exhibiting HLGs at 17q21-23, but not overexpressed.
Our CGH data indicate that OCs have various DNA copy number changes. Among these frequent changes, 17q21-23 may harbor another tumor-associated gene(s) responsible for OC carcinogenesis.
关于卵巢癌（OC）发病机制和/或进展所涉及的分子机制，人们了解甚少。为了研究基因组失衡并确定与该肿瘤相关的癌症相关基因，我们在OC细胞系中应用了比较基因组杂交（CGH）技术。
用CGH分析17个OC细胞系中的染色体畸变情况。由于鉴定出了包括17q21 - 23在内的新染色体区域，我们检测了位于该染色体区域的两个候选基因PS6K和ZNF147的参与情况。我们分别通过荧光原位杂交以及Southern印迹分析和Northern印迹分析检测了这两个候选基因的扩增状态和表达情况。
所有细胞系均显示出大量染色体失衡；最常见的缺失发生在18q22 - 23（29.4%）、13q22 - 34（23.5%）、9p（17.6%）、4p11 - 14（17.6%）和11p14 - 15（17.6%）。最常见的增益出现在20q12 - 13（47.1%）、8q23 - 24（35.2%）、5p15（23.5%）、7q32 - 36（23.5%）和20p（23.5%）。在20q12 - 13（四个细胞系）、8q24（两个细胞系）、12p11 - 12（两个细胞系）和17q21 - 23（两个细胞系）检测到高水平增益（HLGs）。PS6K和ZNF147基因在两个在17q21 - 23表现出HLGs的细胞系中扩增，但未过度表达。
我们的CGH数据表明OC存在各种DNA拷贝数变化。在这些常见变化中，17q21 - 23可能含有另一个负责OC致癌作用的肿瘤相关基因。
