Diep Chieu B, Teixeira Manuel R, Thorstensen Lin, Wiig Johan N, Eknaes Mette, Nesland Jahn M, Giercksky Karl-Erik, Johansson Bertil, Lothe Ragnhild A
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, N-0310 Oslo, Norway.
Mol Cancer. 2004 Feb 23;3:6. doi: 10.1186/1476-4598-3-6.
Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths in the Western world, and despite the fact that metastases are usually the ultimate cause of deaths, the knowledge of the genetics of advanced stages of this disease is limited. In order to identify potential genetic abnormalities underlying the development of local and distant metastases in CRC patients, we have, by comparative genomic hybridization, compared the DNA copy number profiles of 10 primary carcinomas, 14 local recurrences, 7 peritoneal carcinomatoses, and 42 liver metastases from 61 CRC patients.
The median number of aberrations among the primary carcinomas, local recurrences, carcinomatoses, and liver metastases was 10, 6, 13, and 14, respectively. Several genetic imbalances, such as gains of 7, 8q, 13q, and 20, and losses of 4q, 8p, 17p, and 18, were common in all groups. In contrast, gains of 5p and 12p were more common in the carcinomatoses than in other stages of the disease. With hierarchical cluster analysis, liver metastases could be divided into two main subgroups according to clusters of chromosome changes.
Each stage of CRC progression is characterized by a particular genetic profile, and both carcinomatoses and liver metastases are more genetically complex than local recurrences and primary carcinomas. This is the first genome profiling of local recurrences and carcinomatoses, and gains of 5p and 12p seem to be particularly important for the spread of the CRC cells within the peritoneal cavity.
结直肠癌（CRC）是西方世界癌症相关死亡的最常见原因之一，尽管转移通常是最终的死亡原因，但对该疾病晚期遗传学的了解有限。为了确定CRC患者局部和远处转移发生发展的潜在基因异常，我们通过比较基因组杂交技术，比较了61例CRC患者的10例原发性癌、14例局部复发灶、7例腹膜转移癌和42例肝转移灶的DNA拷贝数图谱。
原发性癌、局部复发灶、转移癌和肝转移灶的畸变中位数分别为10、6、13和14。几种基因失衡，如7号、8q、13q和20号染色体的增益，以及4q、8p、17p和18号染色体的缺失，在所有组中都很常见。相比之下，5p和12p的增益在转移癌中比在疾病的其他阶段更常见。通过层次聚类分析，肝转移灶可根据染色体变化聚类分为两个主要亚组。
CRC进展的每个阶段都有其特定的基因特征，转移癌和肝转移灶在遗传上比局部复发灶和原发性癌更复杂。这是首次对局部复发灶和转移癌进行基因组分析，5p和12p的增益似乎对CRC细胞在腹腔内的扩散尤为重要。
