Amplification of a chromatin remodeling gene, Rsf-1/HBXAP, in ovarian carcinoma.
A genomewide technology, digital karyotyping, was used to identify subchromosomal alterations in ovarian cancer. Amplification at 11q13.5 was found in three of seven ovarian carcinomas, and amplicon mapping delineated a 1.8-Mb core of amplification that contained 13 genes. FISH analysis demonstrated amplification of this region in 13.2% of high-grade ovarian carcinomas but not in any of low-grade carcinomas or benign ovarian tumors. Combined genetic and transcriptome analyses showed that Rsf-1 (HBXAPalpha) was the only gene that demonstrated consistent overexpression in all of the tumors harboring the 11q13.5 amplification. Patients with Rsf-1 amplification or overexpression had a significantly shorter overall survival than those without. Overexpression of Rsf-1 gene stimulated cell proliferation and transform nonneoplastic cells by conferring serum-independent and anchorage-independent growth. Furthermore, Rsf-1 gene knockdown inhibited cell growth in OVCAR3 cells, which harbor Rsf-1 amplification. Taken together, these findings indicate an important role of Rsf-1 amplification in ovarian cancer.
Shih
Ie-Ming
IeM
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Sheu
Jim Jinn-Chyuan
JJ
Santillan
Antonio
A
Nakayama
Kentaro
K
Yen
M Jim
MJ
Bristow
Robert E
RE
Vang
Russell
R
Parmigiani
Giovanni
G
Kurman
Robert J
RJ
Trope
Claes G
CG
Davidson
Ben
B
Wang
Tian-Li
TL
D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D002880:Chromosomes, Human, Pair 11; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D015870:Gene Expression; D006801:Humans; D007621:Karyotyping; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
D009687:Nuclear Proteins; C452851:RSF1 protein, human; D015534:Trans-Activators