Shinomiya T, Mori T, Ariyama Y, Sakabe T, Fukuda Y, Murakami Y, Nakamura Y, Inazawa J
Laboratory of Genome Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Japan.
Genes Chromosomes Cancer. 1999 Apr;24(4):337-44.
We investigated copy number aberrations in 29 primary tumors and 12 cell lines of esophageal squamous cell carcinoma (ESC) using comparative genomic hybridization. In the primary tumors, the most common sites of copy number gains were 3q26.3-27 (45%), 8q24 (41%), 5p15 (38%), Xq27-28 (38%), 14q32 (31%), 11q13 (28%), and 20q13.3 (28%). High-level gains (HLGs) indicative of gene amplifications were identified at 11q13 in two cases, and in one case each at 2q33-34, 3q25-29, 5p15.1-15.2, 7q21-22, 11p11.2, 12p11.2-12, and 13q34. Recurrent losses were observed only at 9p13(17.2%). In the 12 ESC cell lines, the most common sites of HLGs were 5p15.1-15.3 (four cases), 11q13 (four cases), 8q24.1-24.2 (three cases), 20q13.2-13.3 (three cases), 3q26.3 (two cases), and 7p15-22 (two cases). Less frequent HLGs (one case each) were observed at 2p16-22, 3q25, 7p12-14, 7q21-22, 9q34, 10q21, 11p11.2, 14q13-14, 14q31-32, 15q22-26, and 17p11.2. Chromosomes and chromosome arms that showed frequent losses in the cultured lines were 18q (58%), 4 (50%), 9p (50%), and 3p (42%). These findings provide evidence for a number of previously unknown genomic aberrations in ESC, suggesting target regions for positional cloning of genes relevant to carcinogenesis in the esophagus. In particular, we identified a significant amplification of the DPI gene (TFDPI), a transcription factor that forms heterodimers with E2FI, in the single primary tumor that exhibited HLG at 13q34.
我们使用比较基因组杂交技术研究了29例食管鳞状细胞癌（ESC）原发性肿瘤和12个细胞系中的拷贝数畸变情况。在原发性肿瘤中，拷贝数增加最常见的位点为3q26.3 - 27（45%）、8q24（41%）、5p15（38%）、Xq27 - 28（38%）、14q32（31%）、11q13（28%）和20q13.3（28%）。在11q13有2例出现了提示基因扩增的高水平扩增（HLG），在2q33 - 34、3q25 - 29、5p15.1 - 15.2、7q21 - 22、11p11.2、12p11.2 - 12和13q34各有1例出现HLG。仅在9p13（17.2%）观察到复发性缺失。在12个ESC细胞系中，HLG最常见的位点为5p15.1 - 15.3（4例）、11q13（4例）、8q24.1 - 24.2（3例）、20q13.2 - 13.3（3例）、3q26.3（2例）和7p15 - 22（2例）。在2p16 - 22、3q25、7p12 - 14、7q21 - 22、9q34、10q21、11p11.2、14q13 - 14、14q31 - 32、15q22 - 26和17p11.2观察到较少见的HLG（各1例）。在培养细胞系中显示频繁缺失的染色体和染色体臂为18q（58%）、4（50%）、9p（50%）和3p（42%）。这些发现为ESC中一些先前未知的基因组畸变提供了证据，提示了食管致癌相关基因定位克隆的靶区域。特别是，我们在13q34出现HLG的单个原发性肿瘤中鉴定出DPI基因（TFDPI）显著扩增，DPI是一种与E2FI形成异二聚体的转录因子。
