Institut de recherche en immunovirologie et cancérologie (IRIC)
Domaine : Cancer
Leukemias represent nearly a third of all cancers diagnosed in children in Canada, and while progress has been made in the treatment of the majority of these leukemias, acute myeloid leukemia (AML) stands out as an exception with a strikingly poor outcome, with only half of all patients being cured. Because the average age of onset of AML is 63, the occurrence of paediatric AML is rare, and suggests that some mutations that carry an increased susceptibility for AML may be inherited in these cases. The hypothesis of this project is that these inherited mutations, in combination with other tumour specific mutations, may allow the atypical development of AML in children. Powerful new DNA sequencing technologies now make it practical to sequence individual patient genomes in order to identify the gene mutations present. This project will use this technology to examine the DNA sequence of the patients tumor and as well as their normal DNA in order to identify tumor specific mutations and novel somatic sequence variants. The DNA of the parents of the patient will also be examined for presence of these same novel somatic sequence variants, along with data from DNA microarrays regarding inherited copy number variations (CNVs) and acquired uniparental disomys (aUPD), in order to study whether inherited genetic changes may play a role in disease development. Having already validated the use of NGS to identify mutations in adult AML samples, the proposed project will build on this established success, while providing valuable novel insight into the biology of this disease in children. This insight will in turn not only enable better patient stratification for treatment, but will also allow the development of novel treatments based on a better understanding of the disease.