Vincent Gagné1, Anne Aubry-Morin1, Maria Plesa1,2, Rachid Abaji1,2, Kateryna Petrykey1,2, Pascal St-Onge1, Patrick Beaulieu1, Caroline Laverdière1,3, Nathalie Alos1,3, Jean-Marie Leclerc1,3, Stephen E Sallan4,5, Donna Neuberg6, Jeffery L Kutok7, Lewis B Silverman4,5, Daniel Sinnett1,3, Maja Krajinovic1,3,2. 1. Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, University of Montreal, Montreal, QC H3T 1C5, Canada. 2. Department of Pharmacology, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada. 3. Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada. 4. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. 5. Division of Hematology/Oncology, Children's Hospital, Boston, MA 02115, USA. 6. Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. 7. Department of Pathology, Brigham & Women's Hospital, Boston, MA 02215, USA.
Abstract
Aim: To evaluate top-ranking genes identified through genome-wide association studies for an association with corticosteroid-related osteonecrosis in children with acute lymphoblastic leukemia (ALL) who received Dana-Farber Cancer Institute treatment protocols. Patients & methods: Lead SNPs from these studies, as well as other variants in the same genes, pooled from whole exome sequencing data, were analyzed for an association with osteonecrosis in childhood ALL patients from Quebec cohort. Top-ranking variants were verified in the replication patient group. Results: The analyses of variants in the ACP1-SH3YL1 locus derived from whole exome sequencing data showed an association of several correlated SNPs (rs11553746, rs2290911, rs7595075, rs2306060 and rs79716074). The rs79716074 defines *B haplotype of the APC1 gene, which is well known for its functional role. Conclusion: This study confirms implication of the ACP1 gene in the treatment-related osteonecrosis in childhood ALL and identifies novel, potentially causal variant of this complication.
Aim: To evaluate top-ranking genes identified through genome-wide association studies for an association with corticosteroid-related osteonecrosis in children with acute lymphoblastic leukemia (ALL) who received Dana-Farber Cancer Institute treatment protocols. Patients & methods: Lead SNPs from these studies, as well as other variants in the same genes, pooled from whole exome sequencing data, were analyzed for an association with osteonecrosis in childhood ALL patients from Quebec cohort. Top-ranking variants were verified in the replication patient group. Results: The analyses of variants in the ACP1-SH3YL1 locus derived from whole exome sequencing data showed an association of several correlated SNPs (rs11553746, rs2290911, rs7595075, rs2306060 and rs79716074). The rs79716074 defines *B haplotype of the APC1 gene, which is well known for its functional role. Conclusion: This study confirms implication of the ACP1 gene in the treatment-related osteonecrosis in childhood ALL and identifies novel, potentially causal variant of this complication.
Entities:
Keywords:
Dana–Farber Cancer Institute cohort; Quebec childhood acute lymploblastic leukemia cohort; acute lymphoblastic leukemia; cosrticosteroids; dexamethasone; osteonecrosis; prednisone; single nucleotide polymorphism
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