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RET-mediated gene expression pattern is affected by isoform but not oncogenic mutation
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Hickey, Jessica G., Myers, Shirley M., Tian, Xuefei, Zhu, Shu Jun, Shaw, Julie L. V., Andrew, Scott D., Richardson, Douglas S., Brettschneider, Julia and Mulligan, Lois M.. (2009) RET-mediated gene expression pattern is affected by isoform but not oncogenic mutation. Genes Chromosomes & Cancer, Vol.48 (No.5). pp. 429-440. ISSN 1045-2257
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Official URL: http://dx.doi.org/10.1002/gcc.20653
Abstract
The inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN 2) is caused by mutations of the RET receptor tyrosine kinase and is characterized by medullary thyroid carcinoma. MEN 2 subtypes have distinct mutational spectrums and vary in severity. The most severe disease subtype, MEN 2B, is associated with a specific RET mutation (M918T) that has been predicted to alter downstream signaling and target gene expression patterns. We used gene expression microarray analysis to identify target genes modulated by RET We compared two oncogenic RET mutants, associated with MEN 2A (2ARET) or MEN 2B (2BRET) disease subtypes, that are predicted to have distinct downstream target genes. We showed that overall, 2ARET and 2BRET modulated genes with similar functional ontologies. Further, when we validated our microarray data by quantitative real time PCR, we did not detect major differences in gene expression associated with these mutants when differences in receptor activity levels were considered. We did, however, detect differences in gene expression induced by two RET COOH-terminal isoforms, RET9 and RETS1, irrespective of the RET form present (wildtype, 2ARET or 2BRET). Our data suggest that similar transcriptional programs contribute to all forms of MEN 2 but that differences in target gene expression may contribute to developmental pattern differences observed between RET isoforms. (C) 2009 Wiley-Liss, Inc.
| Item Type: | Journal Article |
|---|---|
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) Q Science > QH Natural history > QH426 Genetics |
| Divisions: | Faculty of Science > Statistics |
| Journal or Publication Title: | Genes Chromosomes & Cancer |
| Publisher: | Wiley-Liss |
| ISSN: | 1045-2257 |
| Date: | May 2009 |
| Volume: | Vol.48 |
| Number: | No.5 |
| Number of Pages: | 12 |
| Page Range: | pp. 429-440 |
| Identification Number: | 10.1002/gcc.20653 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| Funder: | Canadian Institutes of Health Research, the Canadian Cancer Society through the National Cancer Institute of Canada, Natural Sciences and Engineering Research Council |
| URI: | http://wrap.warwick.ac.uk/id/eprint/28215 |
Data sourced from Thomson Reuters' Web of Knowledge
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