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.digital karyotyping ͉ gene amplification ͉ oncogene

Overexpression of a Chromatin Remodeling Factor, RSF-1/HBXAP, Correlates with Aggressive Oral Squamous Cell Carcinoma

“…In the present study, RSF gene was also found amplified in OSCC (P ϭ 0.042) ( Figure 1C). Similar to the findings in ovarian cancer, 10 OSCC samples with higher RSF-1 DNA copy number tended to show higher expression levels, suggesting that RSF-1 was frequently amplified and overexpressed in OSCC tissues at both the protein and mRNA levels.…”

“…The specificity of anti-RSF-1 antibody for use in IHC has been previously demonstrated. 10,17,18 A positive reaction was defined as discrete localization of the brown chromogen in the nuclei. Immunostaining intensity was independently scored by two investigators using a previously described scoring system 10 ; intensity was recorded as negative (0), weakly positive (1ϩ), moderately positive (2ϩ), strongly positive (3ϩ), or intensely positive (4ϩ).…”

“…10,16,17 Based on the criteria for immunostaining scoring and sample classification in these studies (see Materials and Methods), we stratified cases into two groups: i) with low RSF-1 expression (scores of 0 to ϩ2), and ii) with high RSF-1 expression (scores of ϩ3 or ϩ4).…”

“…10 -12 We have demonstrated that RSF1 is located in the ch11q13.5 region, which is frequently amplified in several types of carcinoma, including ovarian highgrade serous carcinoma. 10,13,14 As compared to other genes within the ch11q13.5 amplicon, RSF1 exhibited the highest correlation between DNA amplification and RNA copy number, and it was responsible for cell growth in the presence of chemotherapeutic agents in ovarian cancer tissues, 10,15 suggesting that RSF1 serves as the "driver" gene within the ch11q13.5 amplicon. RSF-1 overexpression was highly associated with the most aggressive type of ovarian cancer, high-grade serous carcinoma, and shorter overall survival.…”

“…RSF-1 overexpression was highly associated with the most aggressive type of ovarian cancer, high-grade serous carcinoma, and shorter overall survival. 10,16,17 In the current report, we focused on determining the biological significance of RSF-1 expression in oral squamous cell carcinoma (OSCC), the most common oral malignancy. Based on IHC, using a well-characterized antibody, we correlated RSF-1 expression levels with clinicopathological features associated with aggressiveness of the disease.…”