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.

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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