Xiao Xiu-Ying, Zhou Xiao-Yan, Yan Ge, Sun Meng-Hong, Du Xiang
Department of Pathology, Cancer Hospital of Fudan University, Shanghai, China.
Diagn Mol Pathol. 2007 Jun;16(2):96-103. doi: 10.1097/PDM.0b013e31803190f2.
Much information has been reported on the genetic and genomic alterations in colorectal cancer (CRC) in literature; however, nonrandom chromosomal alterations in Chinese CRC patients have only one report in Hong Kong. To further identify genomic alteration in primary sporadic colorectal carcinomas (SCRC) in Chinese patients and understand the molecular mechanisms in CRC development, progress, and metastasis, we used comparative genomic hybridization to screen for losses and/or gains of DNA copies along chromosomes in 24 SCRC tissues from 24 patients. Comparative genomic hybridization was applied to investigate the genomic imbalance in 24 cases of primary SCRC and compared the differences between tumors in different loci and between tumors with and without metastasis. The common chromosomal alterations in the SCRC included gains of chromosomes 1q, 2q, 4q, 7q, 8q, 11q, 13q, 20q and also losses of chromosomes 9p, 16q, 17p, 18q. Among them, gains of 1q, 7q, 20q and losses of 17p, 18q were related with lymph node metastasis of SCRC (P<0.05). The gains of 4q, 7q, 20q and losses of 9p, 18q were related with the sites (P<0.05), colon and rectum, respectively; gain of 20q and loss of 9p were commonly found in the colon cancer; gain of 4q, 7q and loss of 18q were easily seen in the rectal cancer. There are multiple regions of chromosomes with copy-number changes in SCRC. The tumor suppressor genes and oncogenes on these regions may be involved in the development and progress of SCRC. The chromosome 1q, 2q, 4q, 7q, 8q, 11q, 13q, 20q regions may have oncogenes such as epidermal growth factor, MET, platelet-derived growth factor receptor A, and 9p, 16q, 17p, 18q regions may have tumor suppressor genes such as p53,DCC, IGFR1 associated with occurrence of SCRC. The chromosome 1q, 7q, 20q, 17p, 18q regions may have genes related with metastasis of SCRC. The development mechanisms of colon cancer and rectal cancer may not be completely similar. Additionally, gain of chromosome 1q was verified by the second technique-Real-time reverse transcription PCR.
文献中已报道了许多关于结直肠癌（CRC）基因和基因组改变的信息；然而，关于中国CRC患者非随机染色体改变的报道仅见于香港的一篇研究。为了进一步鉴定中国患者原发性散发性结直肠癌（SCRC）中的基因组改变，并了解CRC发生、发展和转移的分子机制，我们使用比较基因组杂交技术对24例患者的24个SCRC组织中的染色体DNA拷贝数的缺失和/或增加进行筛选。应用比较基因组杂交技术研究24例原发性SCRC的基因组失衡情况，并比较不同位点肿瘤之间以及有无转移肿瘤之间的差异。SCRC中常见的染色体改变包括1q、2q、4q、7q、8q、11q、13q、20q染色体的增加以及9p、16q、17p、18q染色体的缺失。其中，1q、7q、20q染色体的增加以及17p、18q染色体的缺失与SCRC的淋巴结转移相关（P<0.05）。4q、7q、20q染色体的增加以及9p、18q染色体的缺失分别与肿瘤部位（P<0.05），即结肠和直肠相关；20q染色体的增加和9p染色体的缺失常见于结肠癌；4q、7q染色体的增加和18q染色体的缺失在直肠癌中较为常见。SCRC中有多个染色体区域存在拷贝数变化。这些区域的抑癌基因和癌基因可能参与了SCRC的发生和发展。1q、2q、4q、7q、8q、11q、13q、20q染色体区域可能存在癌基因，如表皮生长因子、MET、血小板衍生生长因子受体A，而9p、16q、17p、18q染色体区域可能存在抑癌基因，如p53、DCC、IGFR1，与SCRC的发生相关。1q、7q、20q、17p、18q染色体区域可能存在与SCRC转移相关的基因。结肠癌和直肠癌的发生机制可能并不完全相同。此外，通过第二种技术——实时逆转录PCR验证了1q染色体的增加。
