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利用细菌人工染色体阵列比较基因组杂交技术在24种乳腺癌细胞系中检测到常见DNA拷贝数异常的高频率。

High frequency of common DNA copy number abnormalities detected by bacterial artificial chromosome array comparative genomic hybridization in 24 breast cancer cell lines.

作者信息

Saito Soichiro, Morita Keiko, Hirano Takashi

机构信息

Applied Gene Technology Research Group, Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.

出版信息

Hum Cell. 2009 Feb;22(1):1-10. doi: 10.1111/j.1749-0774.2008.00061.x.

Abstract

Breast cancer is a widespread disease in Japan and across the world. Breast cancer cells, as well as most other types of cancer cells, have diverse chromosomal aberrations. Clarifying the character of these chromosomal aberrations should contribute to the development of more suitable therapies, along with the predictions of metastasis and prognosis. Twenty-four breast cancer cell lines were analyzed by bacterial artificial chromosome (BAC) array comparative genomic hybridization (CGH). The array slide contained duplicate spots of 4030 BAC clone DNAs covering the entire human genome with 1 Mbp resolution. In all 24 breast cancer cell lines, frequent and significant amplifications as well as deletions were detected by BAC array CGH. Common DNA copy number gains, detected in 60% (above 15 cell lines) of the 24 breast cancer cell lines were found in 76 BAC clones, located at 1q, 5p, 8q, 9p, 16p, 17q, and 20q. Moreover, common DNA copy number loss was detected in 136 BAC clones, located at 1q, 2q, 3p, 4p, 6q, 8p, 9p, 11p, 13q, 17p, 18q, 19p, Xp, and Xq. The DNA copy number abnormalities found included abnormality of the well-known oncogene cMYC (8q24.21); however, most of them were not reported to relate to breast cancer. BAC array CGH has great potential to detect DNA copy number abnormalities, and has revealed that breast cancer cell lines have substantial heterogeneity.

摘要

乳腺癌在日本乃至全球都是一种广泛存在的疾病。乳腺癌细胞以及大多数其他类型的癌细胞都有多种染色体畸变。阐明这些染色体畸变的特征,应该有助于开发更合适的治疗方法,以及预测转移和预后情况。通过细菌人工染色体(BAC)阵列比较基因组杂交(CGH)对24种乳腺癌细胞系进行了分析。阵列载玻片包含覆盖整个人类基因组的4030个BAC克隆DNA的重复斑点,分辨率为1 Mbp。在所有24种乳腺癌细胞系中,通过BAC阵列CGH检测到频繁且显著的扩增以及缺失。在24种乳腺癌细胞系的60%(超过15个细胞系)中检测到的常见DNA拷贝数增加,存在于位于1q、5p、8q、9p、16p、17q和20q的76个BAC克隆中。此外,在位于1q、2q、3p、4p、6q、8p、9p、11p、13q、17p、18q、19p、Xp和Xq的136个BAC克隆中检测到常见DNA拷贝数缺失。发现的DNA拷贝数异常包括著名的癌基因cMYC(8q24.21)的异常;然而,其中大多数尚未报道与乳腺癌有关。BAC阵列CGH在检测DNA拷贝数异常方面具有巨大潜力,并揭示了乳腺癌细胞系具有显著的异质性。

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