Implication of snoRNA U50 in human breast cancer

• Type of Material: Article
• Authors: Xueyuan Dong, Emory University; Peng Guo, Emory University; Jeff Boyd, Fox Chase Cancer Center; Xiaodong Sun, Emory University; Qunna Li, Emory University; Wei Zhou, Emory University; Jin-Tang Dong, Emory University
• Language: English
• Date: 2009-08
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Institute of Genetics and Developmental Biology and the Genetics Society of China. Published by Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/S1673-8527(08)60134-4
• Title of Journal or Parent Work: Journal of Genetics and Genomics
• ISSN: 1673-8527
• Volume: 36
• Issue: 8
• Start Page: 447
• End Page: 454
• Grant/Funding Information: This work was supported in part by a grant from the National Cancer Institute, USA (No. R01CA085560).
• Keywords: U50; breast cancer; snoRNA; tumor suppressor gene
• Research Categories: Health Sciences, Oncology

Abstract

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.