Barker K T, Crompton M R
Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, UK.
Br J Cancer. 1998 Aug;78(3):296-300. doi: 10.1038/bjc.1998.490.
Activating ras mutations are found in many types of human tumour. Mutations in Harvey (H-), Kirsten (K-) and neuronal (N-) ras are, however, rarely found in breast carcinomas. TC21 is a ras family member that shares close homology to H-, K- and N-ras, and activating mutations have been found in ovarian carcinoma and leiomyosarcoma cell lines. We have examined panels of cDNAs from breast, ovarian and cervical cell lines, and primary and metastatic breast tumours for mutations in TC21 using a single-strand conformational polymorphism (SSCP)-based assay. One breast cancer cell line, CAL51, exhibited an altered SSCP pattern, compared with normal tissue, which was due to an A-T base change in codon 72, causing a predicted Gln-Leu activating mutation. Of nine primary and 15 metastatic breast tumour cDNAs analysed, none exhibited an altered pattern by SSCP. The apparently wild-type pattern by SSCP analysis was confirmed by sequence analysis of some of the cDNAs assayed. Thus, we conclude that mutations in TC21 are uncommon in breast carcinomas.
激活型ras突变见于多种人类肿瘤。然而,哈维(H-)、柯尔斯顿(K-)和神经型(N-)ras的突变在乳腺癌中很少见。TC21是一种ras家族成员,与H-、K-和N-ras具有高度同源性,在卵巢癌细胞系和平滑肌肉瘤细胞系中发现了激活型突变。我们使用基于单链构象多态性(SSCP)的检测方法,检测了来自乳腺、卵巢和宫颈细胞系以及原发性和转移性乳腺肿瘤的cDNA文库中TC21的突变情况。与正常组织相比,一种乳腺癌细胞系CAL51表现出改变的SSCP图谱,这是由于密码子72处的A-T碱基变化,导致预测的Gln-Leu激活突变。在分析的9个原发性和15个转移性乳腺肿瘤cDNA中,通过SSCP均未发现改变的图谱。对一些检测的cDNA进行序列分析证实了SSCP分析显示的明显野生型图谱。因此,我们得出结论,TC21突变在乳腺癌中并不常见。