Somatic Pairing of Chromosome 19 in Renal Oncocytoma is Associated with Deregulated EGLN2-mediated [corrected] Oxygen-sensing Response

Overview

Journal PLoS Genet

Specialty Genetics

Date 2008 Sep 6

PMID 18773095

Citations 39

Authors

Julie M Koeman

Ryan C Russell

Min-Han Tan

David Petillo

Michael Westphal

Katherine Koelzer

Julie L Metcalf

Zhongfa Zhang

Daisuke Matsuda

Karl J Dykema

Heather L Houseman

Eric J Kort

Laura L Furge

Richard J Kahnoski

Stephane Richard

Annick Vieillefond

Pamela J Swiatek

Bin Tean Teh

Michael Ohh

Kyle A Furge

Affiliations

Soon will be listed here.

Abstract

Chromosomal abnormalities, such as structural and numerical abnormalities, are a common occurrence in cancer. The close association of homologous chromosomes during interphase, a phenomenon termed somatic chromosome pairing, has been observed in cancerous cells, but the functional consequences of somatic pairing have not been established. Gene expression profiling studies revealed that somatic pairing of chromosome 19 is a recurrent chromosomal abnormality in renal oncocytoma, a neoplasia of the adult kidney. Somatic pairing was associated with significant disruption of gene expression within the paired regions and resulted in the deregulation of the prolyl-hydroxylase EGLN2 [corrected] a key protein that regulates the oxygen-dependent degradation of hypoxia-inducible factor (HIF). Overexpression of EGLN2 [corrected] in renal oncocytoma increased ubiquitin-mediated destruction of HIF and concomitantly suppressed the expression of several HIF-target genes, including the pro-death BNIP3L gene. The transcriptional changes that are associated with somatic pairing of chromosome 19 mimic the transcriptional changes that occur following DNA amplification. Therefore, in addition to numerical and structural chromosomal abnormalities, alterations in chromosomal spatial dynamics should be considered as genomic events that are associated with tumorigenesis. The identification of EGLN2 as a significantly deregulated gene that maps within the paired chromosome region directly implicates defects in the oxygen-sensing network to the biology of renal oncocytoma.

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