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

• Main Authors: Sonali P. Barwe, Anilkumar Gopalakrisnapillai, Nitin Mahajan, Todd E. Druley, E. Anders Kolb, Erin L. Crowgey
• Format: Article
• Language: English
• Published: Korea Genome Organization 2020-03-01
• Series: Genomics & Informatics
• Subjects: error-corrected sequencing; genomics; patient derived xenograft models; pediatric cancers; structural variants
• Online Access: http://genominfo.org/upload/pdf/gi-2020-18-1-e6.pdf
• ISSN: 2234-0742

Acute leukemia represents the most common pediatric malignancy comprising diverse subtypes with varying prognosis and treatment outcomes. New and targeted treatment options are warranted for this disease. Patient-derived xenograft (PDX) models are increasingly being used for preclinical testing of novel treatment modalities. A novel approach involving targeted error-corrected RNA sequencing using ArcherDX HemeV2 kit was employed 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.