Abstract
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 knock-down 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.
Original language | English (US) |
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Pages (from-to) | 14004-14009 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 102 |
Issue number | 39 |
DOIs | |
State | Published - Sep 27 2005 |
Keywords
- Digital karyotyping
- Gene amplification
- Oncogene
ASJC Scopus subject areas
- General