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Chromosome 19 rearrangements in ovarian carcinomas: zinc finger genes are particularly targeted
Marianne L Smebye1, Anita Sveen, Lisbeth Haugom
1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway.
Abstract:
Chromosome 19 is frequently rearranged in ovarian carcinomas, but the pathogenetic consequences of this are not clearly understood. We performed microarray gene expression analysis on 12 ovarian carcinomas that carry a rearranged chromosome 19 in their karyotype. These aberrant chromosomes have previously been microdissected and analyzed by array-based CGH. In the current study, we wanted to explore whether the genomic alterations thus detected correlated with changes in gene expression. The microarray gene expression analysis gave information on 407 genes mapping in gained genomic regions on chromosome 19, of which 92 showed association between DNA gain and upregulated expression. Of the genes showing this association, 39 (42%) showed gain in at least two samples. The majority of these 39 genes of interest (n = 24, 62%) encode zinc finger proteins, which otherwise make up only 15% of the approximately 1,400 genes on chromosome 19. The strongest association was found for ZNF223 which was upregulated in samples with genomic gain compared with samples without gain. We suggest that DNA copy number changes brought about by rearrangements of chromosome 19 contribute to ovarian carcinogenesis by leading to upregulation of ZNF223 and other zinc finger genes. © 2014 Wiley Periodicals, Inc.
Insights
Rearrangements in chromosome 19 are common in ovarian cancer. Gene expression analysis revealed that gains in chromosome 19 DNA correlate with increased expression of zinc finger genes, including ZNF223, potentially driving cancer development.
Area of Science:
- Genomics
- Cancer Biology
- Molecular Oncology
Background:
- Chromosome 19 rearrangements are frequent in ovarian carcinomas.
- The pathogenetic role of these rearrangements is not fully understood.
- Previous studies identified genomic alterations on chromosome 19 using array-based comparative genomic hybridization (aCGH).
Purpose of the Study:
- To investigate the correlation between genomic alterations on chromosome 19 and gene expression changes in ovarian carcinomas.
- To identify specific genes whose expression is affected by DNA copy number variations on chromosome 19.
- To explore the potential contribution of these gene expression changes to ovarian carcinogenesis.
Main Methods:
- Microarray gene expression analysis was performed on 12 ovarian carcinomas with rearranged chromosome 19.
- Genomic alterations were previously characterized by array-based CGH.
- Correlation analysis was conducted between DNA copy number and gene expression levels for genes on chromosome 19.
Main Results:
- Gene expression analysis identified 407 genes on chromosome 19 with altered copy number.
- Ninety-two genes showed a significant association between DNA gain and upregulated expression.
- A majority of these genes (62%) encode zinc finger proteins, with ZNF223 showing the strongest association between genomic gain and upregulation.
Conclusions:
- Genomic rearrangements of chromosome 19 lead to altered gene expression in ovarian carcinomas.
- Upregulation of zinc finger genes, particularly ZNF223, due to DNA copy number gains may contribute to ovarian carcinogenesis.
- These findings highlight the role of specific genetic alterations on chromosome 19 in the development of ovarian cancer.
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