Centre de recherche
T 514 345-4931, poste 2990
Leukemogenesis and tumor suppressor genes
Oncogenesis is a multistep process that involves the accumulation of mutations in oncogenes and tumor suppressor genes. The short arm of chromosome 12 is affected by genetic rearrangements leading to the loss of genetic material in a wide range of hematological malignancies. It has been shown that chromosome 12p12.3 is associated with a putative tumor suppressor that may play an important in childhood leukemogenesis as well as in certain solid neoplasias. The transcription factor ETV6 is a suitable candidate gene. In this project, we propose to characterize ETV6 by identifying the genes targeted by this transcription repressor in order to build the corresponding regulatory network and by determining the nature of the protein partners involved in the repression complex.
Genetic determinants of childhood leukemia
Sporadic cancer is a complex disease, where the effect of the environment is modulated by a series of genes whose allelic forms represent functional polymorphisms (DNA variants). According to this model, the origin of childhood leukemia could be explained by a combination of genetic susceptibility factors and environmental exposures. Because of the much shorter latency period, the study of pediatric tumors allows a more realistic evaluation of the input of genetic factors and environment exposures during vulnerable periods of development (foetal life and young childhood). In this project, we propose to identify the genetic factors underlying the individual’s susceptibility to childhood leukemia by performing genetic epidemiology studies.
Genetic diversity in regulatory sequences might lead to allelic variation in gene expression levels (quantitative changes). Such variability could alter tightly regulated biological pathways (e.g. cell cycle) and then contribute to change in disease risk. In this project, we propose to determine the extent of genetic variants in regulatory regions and to validate the functional impact of these variants.
- Boily G, Larose J, Langlois S, Sinnett D. Identification of transcripts modulated by ETV6 expression. Br J Haematol. 2007 136:48-62.
- Healy J, Bélanger H, Beaulieu P, Larivière M, Labuda D, Sinnett D. Promoter SNPs in G1/S checkpoint regulators and their impact on the susceptibility to childhood leukemia. Blood. 2007 109:683-92.
- Bélanger H, Beaulieu P, Moreau C, Labuda D, Hudson TJ, Sinnett D. Functional promoter SNPs in cell cycle checkpoint genes. Hum Mol Genet. 2005 14:2641-8.
- Krajinovic M, Lamothe S, Labuda D, Lemieux-Blanchard E, Theoret Y, Moghrabi A, Sinnett D. Role of MTHFR genetic polymorphisms in the susceptibility to childhood acute lymphoblastic leukemia. Blood. 2004 103:252-7.