通过比较基因组杂交和DNA倍体分析结直肠癌肝转移瘤中的基因变化。

Genetic changes in colorectal carcinoma tumors with liver metastases analyzed by comparative genomic hybridization and DNA ploidy.

作者信息

Nakao K, Shibusawa M, Ishihara A, Yoshizawa H, Tsunoda A, Kusano M, Kurose A, Makita T, Sasaki K

机构信息

Second Department of Surgery, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan.

出版信息

Cancer. 2001 Feb 15;91(4):721-6.

PMID:11241239

Abstract

BACKGROUND

Liver metastases are found in 10% of primary colorectal malignancies, and they affects the prognosis of patients with colorectal carcinoma. The authors investigated DNA copy number aberrations by using comparative genomic hybridization (CGH) and DNA ploidy alterations by using flow cytometry (FCM) in patients with primary colorectal carcinoma (primary tumors). To determine whether there are characteristic DNA copy number alterations that contribute to liver metastasis, cytogenetic aberrations were examined by CGH and FCM.

METHODS

The authors analyzed 35 primary tumors, including 16 primary tumors with liver metastasis, by using CGH and FCM.

RESULTS

Increases in DNA copy numbers were detected in 6q (5 of 16 tumors), 7q (6 of 16 tumors), 8q (7 of 16 tumors), 9p (5 of 16 tumors), 13q (8 of 16 tumors), 20p (9 of 16 tumors), and 20q (15 of 16 tumors) in primary tumors with liver metastases. Decreases in DNA copy numbers were found in 17p (5 of 16 tumors), 18p (6 of 19 tumors), 18q (8 of 16 tumors), and 22q (5 of 16 tumors). In contrast, primary tumors without liver metastasis showed gains in chromosome arms 8q (2 of 19 tumors), 13q (2 of 19 tumors), 20p (6 of 19 tumors), and 20q (5 of 19 tumors); however, they showed no gains in 6q or 7q and showed losses in chromosome arms 17p (2 of 19 tumors), 18p (4 of 19 tumors), 18q (6 of 19 tumors), and 22q (5 of 19 tumors). There was a significant difference in the frequency of DNA copy number gains and losses in 6q (P < 0.05), 7q (P < 0.01), 8q (P < 0.05), 13q (P < 0.05), and 20q (P < 0.01), respectively, between primary tumors with and without liver metastases. The differences in the DNA index were not significant between the two groups of primary tumors.

CONCLUSIONS

In liver metastases of primary tumors from patients with colorectal carcinoma, a correlation between DNA copy number aberrations and gains of chromosome arms 6q, 7q, 8q, 13q, and 20q is suggested.

摘要

背景

在10%的原发性结直肠癌中可发现肝转移，其影响结直肠癌患者的预后。作者采用比较基因组杂交（CGH）研究原发性结直肠癌（原发肿瘤）患者的DNA拷贝数畸变，并采用流式细胞术（FCM）研究DNA倍体改变。为确定是否存在导致肝转移的特征性DNA拷贝数改变，通过CGH和FCM检测细胞遗传学畸变。

方法

作者采用CGH和FCM分析了35例原发肿瘤，其中包括16例伴有肝转移的原发肿瘤。

结果

在伴有肝转移的原发肿瘤中，检测到6q（16例肿瘤中的5例）、7q（16例肿瘤中的6例）、8q（16例肿瘤中的7例）、9p（16例肿瘤中的5例）、13q（16例肿瘤中的8例）、20p（16例肿瘤中的9例）和20q（16例肿瘤中的15例）的DNA拷贝数增加。发现17p（16例肿瘤中的5例）、18p（19例肿瘤中的6例）、18q（16例肿瘤中的8例）和22q（16例肿瘤中的5例）的DNA拷贝数减少。相比之下，无肝转移的原发肿瘤显示8q（19例肿瘤中的2例）、13q（19例肿瘤中的2例）、20p（19例肿瘤中的6例）和20q（19例肿瘤中的5例）染色体臂增加；然而，它们在6q或7q未显示增加，且在17p（19例肿瘤中的2例）、18p（19例肿瘤中的4例）、18q（19例肿瘤中的6例）和22q（19例肿瘤中的5例）染色体臂显示减少。伴有和不伴有肝转移的原发肿瘤在6q（P < 0.05）、7q（P < 0.01）、8q（P < 0.05）、13q（P < 0.05）和20q（P < 0.01）的DNA拷贝数增加和减少频率上存在显著差异。两组原发肿瘤的DNA指数差异不显著。