Dyrsø Thomas, Li Jian, Wang Kai, Lindebjerg Jan, Kølvraa Steen, Bolund Lars, Jakobsen Anders, Bruun-Petersen Gert, Li Shengting, Crüger Dorthe G
Department of Clinical Genetics, Vejle Hospital, Denmark.
Cancer Genet. 2011 Feb;204(2):84-95. doi: 10.1016/j.cancergencyto.2010.08.019.
Colorectal cancer (CRC) is one of the most common cancers in Denmark and in the western world in general, and the prognosis is generally poor. According to the traditional molecular classification of sporadic colorectal cancer, microsatellite stable (MSS)/chromosome unstable (CIN) colorectal cancers constitute approximately 85% of sporadic cases, whereas microsatellite unstable (MSI) cases constitute the remaining 15%. In this study, we used array comparative genomic hybridization (aCGH) to identify genomic hotspot regions that harbor recurrent copy number changes. The study material comprised fresh samples from 40 MSS tumors and 20 MSI tumors obtained from 60 Danish CRC patients. We identified five small genomic regions (<15 megabases) exhibiting recurrent copy number loss, which, to our knowledge, have not been reported in previously published aCGH studies of CRC: 3p25.3, 3p21.2-p21.31, 5q13.2, 12q24.23-q24.31, and 12q24.23-q24.31. These regions contain several potentially important tumor suppressor genes that may play a role in a significant proportion of both sporadic MSS CRC and MSI CRC. Furthermore, the generated aCGH data are in support of the recently proposed classification of sporadic CRC into MSS CIN+, MSI CIN-, MSI CIN+, and MSS CIN- cancers.
结直肠癌(CRC)是丹麦以及整个西方世界最常见的癌症之一,其预后通常较差。根据散发性结直肠癌的传统分子分类,微卫星稳定(MSS)/染色体不稳定(CIN)型结直肠癌约占散发性病例的85%,而微卫星不稳定(MSI)型病例占其余的15%。在本研究中,我们使用阵列比较基因组杂交(aCGH)来识别存在反复拷贝数变化的基因组热点区域。研究材料包括从60名丹麦CRC患者身上获取的40个MSS肿瘤和20个MSI肿瘤的新鲜样本。我们识别出五个小基因组区域(<15兆碱基)呈现反复拷贝数缺失,据我们所知,在先前发表的CRC的aCGH研究中尚未报道过这些区域:3p25.3、3p21.2 - p21.31、5q13.2、12q24.23 - q24.31以及12q24.23 - q24.31。这些区域包含几个潜在重要的肿瘤抑制基因,它们可能在相当比例的散发性MSS CRC和MSI CRC中发挥作用。此外,生成的aCGH数据支持最近提出的将散发性CRC分为MSS CIN +、MSI CIN -、MSI CIN +和MSS CIN -癌症的分类方法。