Genom-vid profilering av kandidatgener i leukemi: utforskning av genernes effekt på kemoterapi Genome-wide profiling of candidate genes in leukemia: uncovering host genome effect on chemotherapy

  • Gupta, Ramneek (Project Manager)
  • Abrahamsson, Jonas (Project Participant)
  • Borst, Louise (Project Participant)
  • Jonsson, Olafur Gisli (Project Participant)
  • Schmiegelow, Kjeld (Project Participant)
  • Toft, Nina (Project Participant)
  • Vaitkeviciene, Goda (Project Participant)
  • Wesenberg, Finn (Project Participant)
  • Vettenranta, Kim (Project Participant)

    Project Details

    Description

    Aim: the overall goal is to tailor cancer treatment by genetic profiling of patients, reducing the risk of relapse
    and serious toxic side effects.
    Background: cancer is a leading cause of death in humans (13% worldwide). Furthermore, cancer patients
    differ widely (but unpredictably) in the efficacy of chemotherapy and toxicities they experience. This variation
    in treatment response can to a certain degree be explained by genetic variation between patients. Thus, there
    is a need to explore the genetic diversity of patients in order to improve both drug dosage and identify patients
    at increased risk of specific toxicities.
    Significance for childhood cancer: using childhood acute lymphoblastic leukemia (ALL) as a model cancer and
    applying innovative approaches within bioinformatics and systems biology, we will address the major obstacles
    hitherto faced when exploring the associations between host genomic variants and response to chemotherapy.
    The results obtained will be part of near-future randomized clinical trials in childhood leukemia, investigating
    personalizing chemotherapy.
    Preliminary results, workplan and methods: the present study will perform targeted, but extensive and precise
    genome-wide profiling of clinical relevant single nucleotide polymorphisms (SNPs). Clinical relevant genes and
    SNPs within ALL therapy have been mapped and 35.000 SNPs selected. This panel will now be updated in order
    to fully cover clinical relevant SNPs within areas as drug disposition, immune function and several organ
    toxicities. Furthermore, we wish to improve our in-house targeted multiplexed sequencing platform for
    genotyping, enabling us to cover more of the targeted genome, perform a higher multiplexing and deeper
    sequencing. Finally, we will investigate ALL patients’ genetic profiles in relation to 1) the 20 most common
    serious treatment-related toxicities, 2) early treatment response measured at 3 time points during treatment
    and 3) risk of relapse.
    StatusFinished
    Effective start/end date01/01/201431/12/2018