Impact of chromosome 17q deletion in the primary lesion of colorectal cancer on liver metastasis
Impact of chromosome 17q deletion in the primary lesion of colorectal cancer on liver metastasis
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DOI：
10.3892/ol.2016.5271
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发表时间：
2016-12-01
期刊：
影响因子：
2.9
通讯作者：
Sakamoto, Kazuhiro
中科院分区：
文献类型：
--
作者：
Kawai, Masaya;Komiyama, Hiromitsu;Sakamoto, Kazuhiro
结直肠癌是一种常见的恶性肿瘤，需要研究以阐明潜在的致癌机制。在这些机制中，从头癌变和腺瘤到癌的顺序是最了解的。结直肠癌转移到肝脏往往会导致死亡，因此，重要的是要确定任何相关的风险因素。关于疾病的治疗，重要的是不仅要管理原发性结直肠肿瘤，而且要管理肝转移。以前，通过基因变异分析，染色体丢失已被指示在肝转移中起重要作用。这种分析可能有助于预测肝转移风险，以及个体对治疗的反应，从而改善结直肠癌的管理。在本研究中，我们的目的是澄清的原因。结直肠癌肝转移的比较基因组杂交分析。共分析了2004年至2011年接受手术的晚期结直肠癌患者的116份冷冻样本。本研究分析了位于17和18号染色体上的肿瘤抑制基因非转移基因23（NM 23）（在结直肠癌（DCC）中缺失）和胰腺癌基因座4（DPC 4）中缺失的突变，这些突变均被报道影响结直肠癌的肝转移。采用比较基因组杂交技术研究染色体异常（重复和缺失）与结直肠癌肝转移的关系。聚类分析表明，17号染色体长臂缺失的患者肝转移率最高。同时性和异质性结直肠癌肝转移率与基因变异之间无显著相关性（P=0.206）。然而，当将这些肝转移病例分为同步型和异质型时，根据17q缺失的存在分类的基因变异组之间的每种比例均存在显著差异（P=0.023）。这些结果表明，17 q的缺失可以作为术后状态下肝转移的预测标志物。
Colorectal cancer is a prevalent malignancy worldwide, and investigations are required to elucidate the underlying carcinogenic mechanisms. Amongst these mechanisms, de novo carcinogenesis and the adenoma to carcinoma sequence, are the most understood. Metastasis of colorectal cancer to the liver often results in fatality, therefore, it is important for any associated risk factors to be identified. Regarding the treatment of the disease, it is important to manage not only the primary colorectal tumor, but also the liver metastases. Previously, through gene variation analysis, chromosomal loss has been indicated to serve an important role in liver metastasis. Such analysis may aid in the prediction of liver metastasis risk, alongside individual responses to treatment, thus improving the management of colorectal cancer. In the present study, we aimed to clarify a cause of. the liver metastasis of colorectal cancer using comparative genomic hybridization analysis. A total of 116 frozen samples were analyzed from patients with advanced colorectal cancer that underwent surgery from 2004 to 2011. The present study analyzed mutations within tumor suppressor genes non-metastatic gene 23 (NM23), deleted in colorectal carcinoma (DCC) and deleted in pancreatic carcinoma, locus 4 (DPC4), which are located on chromosomes 17 and 18 and have all been reported to affect liver metastasis of colorectal cancer. The association between chromosomal abnormalities (duplication and deletion) and liver metastasis of colorectal cancer was evaluated using comparative genomic hybridization. Cluster analysis indicated that the group of patients lacking the long arm of chromosome 17 demonstrated the highest rate of liver metastasis. No significant association was observed between the frequency of liver metastases for synchronous and heterochronous colorectal cancer cases and gene variation (P=0.206). However, when these liver metastasis cases were divided into the synchronous and heterochronous types, the ratio of each was significantly different between gene variation groups, classified by the existence of the 17q deletion (P=0.023). These results indicate that the deletion of 17q may act as a predictive marker of liver metastasis in postoperative states.