Implication of snoRNA U50 in human breast cancer

Deletion of chromosome 6q is frequent in breast cancer, and the deletion often involves a region in 6q14-q16. At present, however, theunderlying tumor suppressor gene has not been established. Based on a recent study identifying snoRNA U50 as a candidate for the6q14-16 tumor suppressor gene in prostate cancer, we investigated whether U50 is also involved in breast cancer. PCR-based approachesshowed 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, andthe deletion was both somatic and in germline. Genotyping of a cohort of breast cancer cases and controls for the mutation demonstratedthat, while homozygous genotype of the mutation was rare, its heterozygous genotype occurred more frequently in women with breastcancer. Functionally, re-expression of U50 resulted in the inhibition of colony formation in breast cancer cell lines. These results suggestthat noncoding snoRNA U50 plays a role in the development and/or progression of breast cancer.