Di Martino, E, Taylor, CF, Roulson, J-A et al. (1 more author) (2013) An integrated genomic, transcriptional and protein investigation of FGFRL1 as a putative 4p16.3 deletion target in bladder cancer. Genes Chromosomes and Cancer, 52 (9). pp. 860-871. ISSN 1045-2257
Abstract
Loss of heterozygosity (LOH) of chromosome arm 4p is a common event in bladder and other malignancies. At least three distinct regions of deletion have been identified, but the deletion targets have so far remained elusive. In this study, we have identified a novel region of deletion mapping to 4p16.3 spanning 0–2.1 Mb, in 15% of bladder tumors and 24% of bladder cancer cell lines. FGFRL1, which maps within this region, was investigated as putative deletion target. The retained FGFRL1 allele was not mutated in cell lines and tumors with LOH, although in patients heterozygous for the rs4647930 functional polymorphism, the common allele was preferentially lost in tumor tissue. Epigenetic silencing of the retained allele was also excluded as levels of FGFRL1 mRNA and protein were similar in cell lines and tumors with and without 4p16.3 loss. However, while FGFRL1 protein was moderately expressed in all layers of the normal bladder epithelium, the majority of tumors showed areas of downregulation. Overall, average FGFRL1 protein expression was significantly lower in bladder tumors compared to normal tissue, but downregulation was independent from 4p16.3 LOH status, FGFR3 mutation, and tumor grade and stage. In conclusion, although we found no evidence supporting a “two-hit” inactivation of FGFRL1 in bladder carcinogenesis, the effect of heterozygous deletion coupled with functional polymorphisms, and the role of post-transcriptional downregulation deserves further investigation.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2013 Wiley Periodicals, Inc. This is the peer reviewed version of the following article: Di Martino, E., Taylor, C. F., Roulson, J.-A. and Knowles, M. A. (2013), An integrated genomic, transcriptional and protein investigation of FGFRL1 as a putative 4p16.3 deletion target in bladder cancer. Genes Chromosom. Cancer, 52: 860–871, which has been published in final form at http://dx.doi.org/10.1002/gcc.22082. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Epidemiology and Biostatistics (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Experimental Oncology (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Section of Experimental Oncology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Aug 2016 09:07 |
Last Modified: | 20 Jan 2018 20:24 |
Published Version: | http://dx.doi.org/10.1002/gcc.22082 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/gcc.22082 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:86567 |