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.
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Acknowledgements
We thank Dr Frank Speleman for kindly providing us with the neuroblastoma cell lines, Dr Manuela Campiglio for breast cancer cell lines, and Dr Mariano Rocchi for free distribution of FISH probes (http://www.biologia.uniba.it/rmc). We are grateful to Mrs Silvia Grassi for the editing of the manuscript. This work was partially supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) and by Ministero della salute.
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Modena, P., Testi, M., Facchinetti, F. et al. 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 22, 4586–4593 (2003). https://doi.org/10.1038/sj.onc.1206472
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DOI: https://doi.org/10.1038/sj.onc.1206472
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