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


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 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.

SUBMITTER: Shih IeM 

PROVIDER: S-EPMC1236547 | biostudies-literature | 2005 Sep

REPOSITORIES: biostudies-literature

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

Shih Ie-Ming IeM   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  

Proceedings of the National Academy of Sciences of the United States of America 20050919 39


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 (  ...[more]

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