Journal article
Cost-effective multiplexing before capture allows screening of 25 000 clinically relevant SNPs in childhood acute lymphoblastic leukemia
Department of Systems Biology, Technical University of Denmark1
Copenhagen University Hospital Herlev and Gentofte2
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark3
University of Copenhagen4
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark5
CFB - Metagenomic Systems Biology, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark6
Genetic variants, including single-nucleotide polymorphisms (SNPs), are key determiners of interindividual differences in treatment efficacy and toxicity in childhood acute lymphoblastic leukemia (ALL). Although up to 13 chemotherapeutic agents are used in the treatment of this cancer, it remains a model disease for exploring the impact of genetic variation due to well-characterized cytogenetics, drug response pathways and precise monitoring of minimal residual disease.
Here, we have selected clinically relevant genes and SNPs through literature screening, and on the basis of associations with key pathways, protein-protein interactions or downstream partners that have a role in drug disposition and treatment efficacy in childhood ALL. This allows exploration of pathways, where one of several genetic variants may lead to similar clinical phenotypes through related molecular mechanisms.
We have designed a cost-effective, high-throughput capture assay of â¼25â000 clinically relevant SNPs, and demonstrated that multiple samples can be tagged and pooled before genome capture in targeted enrichment with a sufficient sequencing depth for genotyping. This multiplexed, targeted sequencing method allows exploration of the impact of pharmacogenetics on efficacy and toxicity in childhood ALL treatment, which will be of importance for personalized chemotherapy.Leukemia advance online publication, 18 March 2011; doi:10.1038/leu.2011.32.
Language: | English |
---|---|
Publisher: | Nature Publishing Group UK |
Year: | 2011 |
Pages: | 1001-1006 |
ISSN: | 14765551 and 08876924 |
Types: | Journal article |
DOI: | 10.1038/leu.2011.32 |
ORCIDs: | 0000-0003-0316-5866 , 0000-0003-2762-1002 and Gupta, Ramneek |
Childhood acute lymphoblastic leukemia Clinically relevant SNPs Multiplexed genotyping Next-generation sequencing SDG 3 - Good Health and Well-being Target-enrichment
Adolescent Child, Preschool Cost-Benefit Analysis Genotype High-Throughput Nucleotide Sequencing Humans Infant Infant, Newborn Pharmacogenetics Phenotype Polymorphism, Single Nucleotide Precursor Cell Lymphoblastic Leukemia-Lymphoma Treatment Outcome childhood acute lymphoblastic leukemia clinically relevant SNPs multiplexed genotyping next-generation sequencing target-enrichment