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, 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.
Dong
Xue-Yuan
XY
Department of Hematology and Medical Oncology and Winship Cancer Institute, Emory University School of Medicine, 1365 Clifton Road, Atlanta, Georgia 30322, USA.
Guo
Peng
P
Boyd
Jeff
J
Sun
Xiaodong
X
Li
Qunna
Q
Zhou
Wei
W
Dong
Jin-Tang
JT
D000483:Alleles; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D009154:Mutation; D020537:RNA, Small Nucleolar / Q000235:genetics*; D012307:Risk Factors; D014158:Transcription, Genetic
D020537:RNA, Small Nucleolar
Nat Rev Mol Cell Biol. 2007 Mar;8(3):209-20
17318225
Oncogene. 2003 May 15;22(19):2972-83
12771949
BMC Cancer. 2006 Apr 12;6:92
16608533
Cancer Res. 2000 Jul 15;60(14):3880-3
10919663
CA Cancer J Clin. 2007 Mar-Apr;57(2):90-104
17392386
Int J Cancer. 2001 Jul 1;93(1):80-4
11391625
Clin Cancer Res. 1996 Sep;2(9):1601-6
9816339
Cancer Res. 1990 May 1;50(9):2724-8
2328498
J Natl Cancer Inst. 1989 Dec 6;81(23):1780-6
2685334
Nat Rev Genet. 2004 Apr;5(4):316-23
15131654
Int J Oncol. 2000 Dec;17(6):1125-9
11078797
Br J Cancer. 1993 Mar;67(3):551-9
8094976
Oncogene. 1991 Sep;6(9):1705-11
1681492
Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4340-5
18326623
Hum Mol Genet. 2008 Apr 1;17(7):1031-42
18202102
Br J Cancer. 1995 Feb;71(2):290-3
7841042
Mol Cancer Res. 2005 Sep;3(9):483-92
16179495
Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R121-32
15809264
J Biol Chem. 2003 Feb 21;278(8):6041-9
12473647
Cancer Genet Cytogenet. 1990 Oct 15;49(2):203-17
2170003
Br J Cancer. 1998 Sep;78(6):806-11
9743305
Am J Pathol. 1999 Sep;155(3):683-94
10487825
Oncogene. 1996 Jan 18;12(2):247-52
8570202
Br J Cancer. 1996 Jan;73(2):144-7
8546898
Genes Chromosomes Cancer. 2000 Jan;27(1):76-84
10564589
Oncogene. 2007 Sep 13;26(42):6220-8
17384672
Cancer Res. 2006 Jul 15;66(14):6998-7006
16849544
Science. 2006 Jan 13;311(5758):230-2
16357227
Cancer Res. 1997 Jul 1;57(13):2765-80
9205089
Proc Natl Acad Sci U S A. 2003 May 13;100(10):5956-61
12719539
Oncogene. 1996 Aug 15;13(4):677-85
8761288
Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8835-40
9671765
Mol Cell Biol. 1998 Dec;18(12):6897-909
9819378
Hum Genet. 1998 Dec;103(6):727-9
9921911
Oncogene. 2009 Jan 15;28(2):195-208
18836484
Nat Genet. 2005 Apr;37(4):407-12
15750593
Am J Hum Genet. 2009 Feb;84(2):115-22
19147119
Cancer Metastasis Rev. 2001;20(3-4):173-93
12085961