Dong Xue-Yuan, Guo Peng, Boyd Jeff, Sun Xiaodong, Li Qunna, Zhou Wei, Dong Jin-Tang
Department of Hematology and Medical Oncology and Winship Cancer Institute, Emory University School of Medicine, 1365 Clifton Road, Atlanta, Georgia 30322, USA.
J Genet Genomics. 2009 Aug;36(8):447-54. doi: 10.1016/S1673-8527(08)60134-4.
Deletion of chromosome 6q is frequent in breast cancer, and the deletion often involves a region in 6q14-q16. At present, however, the underlying tumor suppressor gene has not been established. Based on a recent study identifying snoRNA U50 as a candidate for the 6q14-16 tumor suppressor gene in prostate cancer, we investigated whether U50 is also involved in breast cancer. PCR-based approaches showed that U50 underwent frequent genomic deletion and transcriptional downregulation in cell lines derived from breast cancer. Mutation screening identified the same 2-bp deletion of U50 as in prostate cancer in both cell lines and primary tumors from breast cancer, and the deletion was both somatic and in germline. Genotyping of a cohort of breast cancer cases and controls for the mutation demonstrated that, while homozygous genotype of the mutation was rare, its heterozygous genotype occurred more frequently in women with breast cancer. Functionally, re-expression of U50 resulted in the inhibition of colony formation in breast cancer cell lines. These results suggest that noncoding snoRNA U50 plays a role in the development and/or progression of breast cancer.
6号染色体长臂缺失在乳腺癌中很常见，且该缺失常累及6q14 - q16区域。然而，目前其潜在的肿瘤抑制基因尚未明确。基于最近一项研究确定小核仁RNA U50为前列腺癌6q14 - 16肿瘤抑制基因的候选基因，我们研究了U50是否也与乳腺癌有关。基于聚合酶链反应的方法显示，U50在乳腺癌细胞系中频繁发生基因组缺失和转录下调。突变筛查在乳腺癌细胞系和原发性肿瘤中均发现了与前列腺癌相同的U50 2个碱基的缺失，且该缺失在体细胞和种系中均存在。对一组乳腺癌病例和对照进行该突变的基因分型表明，虽然该突变的纯合基因型罕见，但其杂合基因型在乳腺癌女性中出现得更频繁。在功能上，U50的重新表达导致乳腺癌细胞系中集落形成受到抑制。这些结果表明，非编码小核仁RNA U50在乳腺癌的发生发展和/或进展中起作用。
