InvolvementofcyclinD3inlivermetastasisofcolorectal.pptVIP

Involvement of cyclin D3 in liver metastasis of colorectal cancer, revealed by genome-wide copy-number analysis Laboratory Investigation (2005) 85, 1118-1129. doi:10.1038/labinvest.3700312; published online 27 June 2005 ABSTRACT subtractive comparative genomic hybridization (CGH) for 20 CRC patients Analysis of 11 CRC cell lines using array-based CGH (CGH-array) Quantitative RT-PCR showed that CCND3 was significantly upregulated in liver-metastatic lesions compared with primary lesions immunohistochemical analysis of 120 primary CRC tumors Comparative Genomic Hybridization (CGH) 比較基因體雜交法1992 CGH is a molecular cytogenetic method of screening a tumor for genetic changes. CGH原理 原理是把胚胎細胞的DNA 抽取出來，標上特定的螢光（一般用綠光），再與標上另一特定螢光（一般是用紅光）。以此二者為探針，雜交到製備好的分裂中期染色體上 如果胚胎細胞DNA 與正常細胞基因等量，雜交後對應的染色體區域便呈黃色。 如果胚胎細胞DNA 有放大的情況，那麼染色體該特定區域便會變得偏綠色 如果胚胎細胞DNA 有缺失，那麼染色體雜交後對應的區域會變得偏紅色。 Conventional CGH in 20 primary tumors. Regions with the most frequent copy-number gains in primary tumors were at 13q (70%), 20q (65%), 8q (55%), 20p (40%), 7p and 7q (25% each), and 1q (20%). losses in primary tumors were seen at 18q (55%), 18p and 8p (50% each), 1p (40%), 17p (35%), 4q (30%), 4p (25%), and 3p (35%) Conventional CGH in liver metastases of the same tumors Common regions for the most frequent copy-number gains in metastatic tumors were at 8q (70%), 20q and 13q (60% each), 20p (45%), 7p (40%), 7q (35%), Xq (25%), 1q (20%), and 6p (15%). losses in metastatic tumors were seen at 8p (60%), 18p and 18q (55% each), 14q (30%), 17p (25%), 4p and 22q (20% each), 4q (15%), and 1p (15%). subtractive (CGH) subtractive CGH結果 our direct comparisons of 20 paired samples by means of subtractive CGH analysis identified gain in 6p as a metastasis-specific change, but we found no significant differences at chromosomes 7, 8, 13, 18, or 20, where major chromosomal aberrations occurred in both primary and metastatic tumors CGH之重要性 CGH 可以針對整個染色體進行全面性的比對，解析度最好可高達1M bp 其解析度雖較FISH 差，但卻能同時偵測23 對染色體的異常