Skip Navigation


Human Molecular Genetics Advance Access originally published online on August 4, 2005
Human Molecular Genetics 2005 14(18):2641-2648; doi:10.1093/hmg/ddi298
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Material
Right arrow All Versions of this Article:
14/18/2641    most recent
ddi298v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (5)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Bélanger, H.
Right arrow Articles by Sinnett, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bélanger, H.
Right arrow Articles by Sinnett, D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Functional promoter SNPs in cell cycle checkpoint genes

Hélène Bélanger1, Patrick Beaulieu1, Claudia Moreau1, Damian Labuda1,2, Thomas J. Hudson3 and Daniel Sinnett1,2,*

1Division of Hematology–Oncology, Research Center, Sainte-Justine Hospital, 3175 chemin de la Côte-Sainte-Catherine, Montreal, Canada QC H3T 1C5, 2Department of Pediatrics, University of Montreal, 3175 Côte-Sainte-Catherine, Montreal, Canada QC H3T 1C5 and 3McGill University and Genome Quebec Innovation Centre, 740 Drive Penfield Avenue, Montreal, Canada QC H3A 1A4

* To whom correspondence should be addressed. Tel: +1 5143454931 ext. 2990; Fax: +1 5143454731; Email: daniel.sinnett{at}umontreal.ca

Received June 2, 2005; Revised August 1, 2005; Accepted August 1, 2005

A substantial number of genes mutated in human cancers encode components of the cell cycle processes. As the G1/S transition in the cell cycle is a finely regulated biological process, we hypothesized that sequence variations in the promoter region of the related genes might indeed lead to abnormal expression, thus predisposing the individuals carrying these genetic variants to cancer. In this report, we screened the promoter regions of 16 cell cycle checkpoint genes for DNA variants and assessed the functional impact of these promoter region single nucleotide polymorphisms (pSNPs) by combining in silico analysis and in vitro functional assays. We identified 127 pSNPs including 90 with predicted impact on putative binding sites of known transcription factors. Eleven pSNPs were selected for electrophoresis mobility shift assays because of their association with predicted gains of binding sites, and nine pSNPs showed differential allelic shifts in at least one cell line tested. Following the subcloning of the promoter regions into a gene reporter system, we found that at least four promoter haplotypes associated with CCND1, E2F1, HDAC1 and RB1 significantly influenced transcriptional activity in an allele-specific manner. Although the biological significance of these observations still remains to be demonstrated, the expected variability of expression levels in key cell cycle components might influence individual's risk of cancer.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 JCOHome page
F. Graziano, A. Ruzzo, F. Loupakis, E. Canestrari, D. Santini, V. Catalano, R. Bisonni, U. Torresi, I. Floriani, G. Schiavon, et al.
Pharmacogenetic Profiling for Cetuximab Plus Irinotecan Therapy in Patients With Refractory Advanced Colorectal Cancer
J. Clin. Oncol., March 20, 2008; 26(9): 1427 - 1434.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. Healy, H. Belanger, P. Beaulieu, M. Lariviere, D. Labuda, and D. Sinnett
Promoter SNPs in G1/S checkpoint regulators and their impact on the susceptibility to childhood leukemia
Blood, January 15, 2007; 109(2): 683 - 692.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.