Jiang Jeng-Kai, Chen Yann-Jang, Lin Chi-Hung, Yu I-Ting, Lin Jen-Kou
Division of Colorectal Surgery, Department of Surgery, Veterans General Hospital-Taipei and National Yang-Ming University, Taiwan.
Genes Chromosomes Cancer. 2005 May;43(1):25-36. doi: 10.1002/gcc.20167.
About 10% of colorectal carcinoma patients develop pulmonary metastases during their lifetime. We address whether and how the chromosomal abnormalities differ between the primary cancers and their metastatic counterparts, what the clonality relationship (CR) is between them, and whether certain genomic aberrations contribute to this disease progression. Comparative genomic hybridization (CGH) experiments were performed on 18 paired samples of primary and pulmonary metastases obtained from patients who had undergone two consecutive surgeries and from whom clinical data had been collected. The CGH profiles also were used as indexes for determining the CR between the cancers. The overall CGH abnormality profiles were similar for the primary colorectal carcinomas and their pulmonary metastases. Frequent gains were found on chromosome arms 20q, 8q, 13q, and 7q, whereas common losses were found on 18q, 8p, and 18p. The pulmonary metastases, however, contained more CGH abnormalities than did the primary carcinomas (total aberration events per tumor: 12.6 +/- 5.0 vs. 8.3 +/- 5.7, respectively, P = 0.024; gains: 7.6 +/- 3.1 vs. 5.1 +/- 3.5, respectively, P = 0.036; losses: 5.0 +/- 2.8 vs. 3.3 +/- 2.9, respectively, P = 0.076). Comparing CGH profiles between individual primary and metastasis pairs, we found that 10 of the 18 (56%) paired samples examined exhibited a high degree of CR, indicating that they were likely to have originated from the same clone and/or that not many additional chromosomal changes had occurred in the metastases, except for 4q loss, whose incidence was much higher in the metastases than in the primaries (60% vs. 10%; P = 0.030). Also, the primary tumors of the high-CR group carried more genomic aberrations, especially 8p loss, than did the primary tumors in the low-CR group. We found more chromosomal changes associated with the pulmonary metastases of colorectal cancer compared with the corresponding primary tumors. We concluded that primary cancers containing more genomic lesions, especially 8p losses, are more likely to metastasize to the lungs. Loss of 4q is potentially a supplementary factor contributing to the dissemination of this disease.
约10%的结直肠癌患者在其一生中会发生肺转移。我们探讨原发性癌症与其转移灶之间的染色体异常是否存在差异以及如何存在差异，它们之间的克隆性关系（CR）是什么，以及某些基因组畸变是否促成了这种疾病进展。对18对原发性和肺转移灶样本进行了比较基因组杂交（CGH）实验，这些样本来自接受了两次连续手术且已收集临床数据的患者。CGH图谱也被用作确定癌症之间CR的指标。原发性结直肠癌及其肺转移灶的总体CGH异常图谱相似。在染色体臂20q、8q、13q和7q上发现频繁的增益，而在18q、8p和18p上发现常见的缺失。然而，肺转移灶比原发性癌包含更多的CGH异常（每个肿瘤的总畸变事件：分别为12.6±5.0和8.3±5.7，P = 0.024；增益：分别为7.6±3.1和5.1±3.5，P = 0.036；缺失：分别为5.0±2.8和3.3±2.9，P = 0.076）。比较单个原发性和转移灶配对样本之间的CGH图谱，我们发现所检测的18对（56%）配对样本中有10对表现出高度的CR，表明它们可能起源于同一克隆，和/或转移灶中除了4q缺失外没有发生太多额外的染色体变化，4q缺失在转移灶中的发生率远高于原发性癌（60%对10%；P = 0.030）。此外，高CR组的原发性肿瘤比低CR组的原发性肿瘤携带更多的基因组畸变，尤其是8p缺失。与相应的原发性肿瘤相比，我们发现与结直肠癌肺转移相关的染色体变化更多。我们得出结论，包含更多基因组病变，尤其是8p缺失的原发性癌更有可能转移至肺部。4q缺失可能是促成这种疾病播散的一个补充因素。
