Beyond the Identification of Transcribed Sequences:
Functional, Evolutionary and Expression Analysis
12th International Workshop
October 25-28, 2002
Washington, DC


List of Abstracts * Speakers * Organizers * Authors * Original Announcement


Functional Characterization of ETV6, a Candidate Tumor Suppressor Gene Associated with Childhood Acute Lymphoblastic Leukaemia

Gino Boily1 and Daniel Sinnett1,2
1Research Center, Sainte-Justine Hospital; 2Department of Pediatrics, University of Montreal, Montreal, QC Canada
Telephone: 514-345-4931-6142
Fax: 514-345-4731
Email: gino_boily@hotmail.com

Deletion of the 12p12 locus is a frequent genetic abnormality observed in childhood pre-B acute lymphoblastic leukemia (ALL), suggesting the presence of a tumor suppressor gene in the region.  In most cases, these deletions are associated with the translocation t(12;21) on the non-deleted allele, resulting in the expression of the fusion protein ETV6-AML1 and in the inactivation of the ETV6 gene.  ETV6 encodes a member of the Ets family of transcription factors and may play a role as a transcriptional repressor.  In the present study, we want to evaluate the functional impact of the expression of ETV6 by overexpression or knock down experiments.  ETV6 cDNA was stably transfected into a pre-B ALL cell line possessing the translocation t(12;21) and expressing the related fusion protein ETV6-AML1 but not ETV6.  We found that the doubling time of the ETV6-transfected cells was increased by 12% as compared to the vector alone-transfected cells (p = 0.008).  The heterogeneous ETV6-transfected population weakly expressed ETV6, and out of the 11 clones generated from this population, none strongly expressed ETV6. All together, these data suggest that a negative selection of ETV6 expressing-cells is operating and support the hypothesis that ETV6 may act as a tumor suppressor gene.  We are now generating cellular models, by the means of inducible systems and RNAi technology, in which we will be able to modulate the expression status of ETV6 in combination with the presence of ETV6-AML1 or not.  Our preliminary data show that ETV6 can be silenced efficiently in HeLa and NIH 3T3 cells by transfection of siRNA.  These cellular models will help us to understand the role of ETV6 and to eventually identify target genes of this transcription factor.



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