Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Tokyo, Japan.
Genes Chromosomes Cancer. 2010 May;49(5):487-96. doi: 10.1002/gcc.20759.
In colorectal cancer (CRC) care, treatment decisions depend on the efforts to estimate the metastatic potential of tumors. The liver is one of the most common metastatic sites of CRC and the prognosis of CRC patients often reflects metastases to distant sites. To identify chromosomal aberrations associated with liver metastasis, we performed allelic copy number analysis for CRC with or without synchronous liver metastasis using genotyping arrays. By allelic copy number analysis of CRC samples, we observed common aberrations in 14 chromosomal arms in two groups, that is, gains on 7p22.3-p11.2, 8q22.3-q24.3, 13q12.12-q34, and 20q11.22-q13.33 and loss of heterozygosity (LOH) on 4q12-q35.1, 5q11.2-q35.3, 8p23.3-p12, 15q11.2-q26.3, 17p13.3-p11.2, 17q11.2-q25.1, 18p11.32-p11.21, 18q11.2-q23, 20p13-p12.1, and 22q11.1-q13.32. We found that gains on 20p13-p12.1 and 20q11.21-q13.33 and LOH on 6q14.1-q25.1 were more frequent in CRC with liver metastasis. We also compared chromosomal aberrations in primary CRC lesions with those of the corresponding liver metastasis and found that the allelic genome imbalance status of a metastatic lesion is similar to that of the primary cancer, which suggests that chromosomal aberrations are largely maintained on hematogenous spread. Intriguingly, several chromosomal aberrations in CRC were found in the primary cancer but not in the corresponding liver metastasis, thus suggesting heterogeneity of cancer cells within solid tumors or the presence of events uniquely developed in primary tumors. Consequently, CRC with and without liver metastasis harbor similar chromosomal aberrations, and chromosomal aberration at 6q, 20p, and 20q may be involved in the process of liver metastasis of CRC.
在结直肠癌(CRC)的治疗中,治疗决策取决于评估肿瘤转移潜能的努力。肝脏是 CRC 最常见的转移部位之一,CRC 患者的预后通常反映了远处转移。为了鉴定与肝转移相关的染色体畸变,我们使用基因分型阵列对伴有或不伴有同步肝转移的 CRC 进行了等位基因拷贝数分析。通过对 CRC 样本的等位基因拷贝数分析,我们观察到两组中 14 条染色体臂上的常见畸变,即 7p22.3-p11.2、8q22.3-q24.3、13q12.12-q34 和 20q11.22-q13.33 的增益以及 4q12-q35.1、5q11.2-q35.3、8p23.3-p12、15q11.2-q26.3、17p13.3-p11.2、17q11.2-q25.1、18p11.32-p11.21、18q11.2-q23、20p13-p12.1 和 22q11.1-q13.32 的杂合性缺失(LOH)。我们发现,CRC 伴有肝转移时,20p13-p12.1 和 20q11.21-q13.33 的增益以及 6q14.1-q25.1 的 LOH 更为频繁。我们还比较了原发性 CRC 病变与相应肝转移的染色体畸变,发现转移灶的等位基因基因组失衡状态与原发性癌症相似,这表明染色体畸变在血源性播散过程中基本保持不变。有趣的是,在原发性癌症中发现了一些 CRC 染色体畸变,但在相应的肝转移中没有发现,这表明实体瘤内的癌细胞存在异质性,或者原发性肿瘤中存在独特的事件。因此,伴有或不伴有肝转移的 CRC 具有相似的染色体畸变,6q、20p 和 20q 上的染色体畸变可能参与了 CRC 的肝转移过程。