Strong concordance between RNA structural and single nucleotide variants identified via next generation sequencing techniques in primary pediatric leukemia and patient-derived xenograft samples

Sonali P. Barwe, Anilkumar Gopalakrisnapillai, Nitin Mahajan, Todd E. Druley, E. Anders Kolb, Erin L. Crowgey

Research output: Contribution to journalArticlepeer-review

Abstract

Acute leukemia represents the most common pediatric malignancy comprising diverse sub-types with varying prognosis and treatment outcomes. New and targeted treatment op-tions are warranted for this disease. Patient-derived xenograft (PDX) models are increas-ingly being used for preclinical testing of novel treatment modalities. A novel approach in-volving targeted error-corrected RNA sequencing using ArcherDX HemeV2 kit was em-ployed to compare 25 primary pediatric acute leukemia samples and their corresponding PDX samples. A comparison of the primary samples and PDX samples revealed a high concordance between single nucleotide variants and gene fusions whereas other complex structural variants were not as consistent. The presence of gene fusions representing the major driver mutations at similar allelic frequencies in PDX samples compared to primary samples and over multiple passages confirms the utility of PDX models for preclinical drug testing. Characterization and tracking of these novel cryptic fusions and exonal variants in PDX models is critical in assessing response to potential new therapies.

Original languageEnglish
Article numbere6
JournalGenomics and Informatics
Volume18
Issue number1
DOIs
StatePublished - Mar 2020

Keywords

  • Error-corrected sequencing
  • Genomics
  • Patient derived xenograft models
  • Pediatric cancers
  • Structural variants

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