UQCRH gene encoding mitochondrial Hinge protein is interrupted by a translocation in a soft-tissue sarcoma and epigenetically inactivated in some cancer cell lines

Oncogene. 2003 Jul 17;22(29):4586-93. doi: 10.1038/sj.onc.1206472.

Abstract

We previously reported the identification of a novel zinc-finger gene, designated ZSG, fused to Ewing sarcoma gene (EWS) by a submicroscopic paracentric inversion of 22q12 in a small round cell sarcoma presenting a translocation t(1;22)(p34;q12). We report here the molecular cloning and characterization of the breakpoint in 1p34, which encompasses the gene coding for mitochondrial Hinge protein ubiquinol-cytochrome C reductase hinge gene (UQCRH). All the three breakpoints, two on 22q12 and one in 1p34, interrupt different genes: EWS, ZSG and UQCRH. We determined the genomic structure of UQCRH, characterized its splicing variants and identified a transcribed processed pseudogene. The analysis of UQCRH expression in normal tissues and cancer cell lines revealed absent expression of UQCRH in two ovarian and one breast cancer cell lines and reduced expression in a further breast carcinoma cell line. CpG island methylation upstream exon 1 was detected in all the three cell lines with absent expression. Moreover, treatment with demethylating agent 5-azacytidine restored UQCRH expression in OAW42 ovarian cancer cells. These data provide preliminary evidence of the inactivation of UQCRH gene in cancer either by structural rearrangements or epigenetic mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Azacitidine / pharmacology
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Chromosomes, Human, Pair 1
  • Chromosomes, Human, Pair 22
  • CpG Islands
  • DNA Methylation
  • DNA-Binding Proteins
  • Electron Transport Complex III
  • Exons
  • Extrachromosomal Inheritance
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Humans
  • Kruppel-Like Transcription Factors
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics*
  • Promoter Regions, Genetic
  • Proteins / genetics*
  • Proteins / metabolism
  • RNA-Binding Protein EWS / genetics
  • Repressor Proteins*
  • Sarcoma / genetics*
  • Soft Tissue Neoplasms / genetics*
  • Translocation, Genetic / genetics*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Kruppel-Like Transcription Factors
  • Neoplasm Proteins
  • PATZ1 protein, human
  • Proteins
  • RNA-Binding Protein EWS
  • Repressor Proteins
  • UQCRH protein, human
  • Electron Transport Complex III
  • Azacitidine