JOURNAL ARTICLE

Amplification of a chromatin remodeling gene, Rsf-1/HBXAP, in ovarian carcinoma

Ie-Ming Shih, Jim Jinn-Chyuan Sheu, Antonio Santillan, Kentaro Nakayama, M Jim Yen, Robert E Bristow, Russell Vang, Giovanni Parmigiani, Robert J Kurman, Claes G Trope, Ben Davidson, Tian-Li Wang
Proceedings of the National Academy of Sciences of the United States of America 2005 September 27, 102 (39): 14004-9
16172393
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.

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