Strong concordance between RNA structural and single nucleotide variants identified via next generation sequencing techniques in primary pediatric leukemia and patient-derived xenograft samples
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 n...
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| Language: | English |
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BioMed Central
2020-03-01
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| Series: | Genomics & Informatics |
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| Online Access: | http://genominfo.org/upload/pdf/gi-2020-18-1-e6.pdf |
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| author | Sonali P. Barwe Anilkumar Gopalakrisnapillai Nitin Mahajan Todd E. Druley E. Anders Kolb Erin L. Crowgey |
| author_facet | Sonali P. Barwe Anilkumar Gopalakrisnapillai Nitin Mahajan Todd E. Druley E. Anders Kolb Erin L. Crowgey |
| author_sort | Sonali P. Barwe |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-eee48c9c0186465c9c42dd38b11b285a |
| institution | Kabale University |
| issn | 2234-0742 |
| language | English |
| publishDate | 2020-03-01 |
| publisher | BioMed Central |
| record_format | Article |
| series | Genomics & Informatics |
| spelling | doaj-art-eee48c9c0186465c9c42dd38b11b285a2025-02-02T09:28:51ZengBioMed CentralGenomics & Informatics2234-07422020-03-0118110.5808/GI.2020.18.1.e6596Strong concordance between RNA structural and single nucleotide variants identified via next generation sequencing techniques in primary pediatric leukemia and patient-derived xenograft samplesSonali P. Barwe0Anilkumar Gopalakrisnapillai1Nitin Mahajan2Todd E. Druley3E. Anders Kolb4Erin L. Crowgey5 Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA Washington University School of Medicine, St. Louis, MO 63110, USA Washington University School of Medicine, St. Louis, MO 63110, USA Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USAAcute 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.http://genominfo.org/upload/pdf/gi-2020-18-1-e6.pdferror-corrected sequencinggenomicspatient derived xenograft modelspediatric cancersstructural variants |
| spellingShingle | Sonali P. Barwe Anilkumar Gopalakrisnapillai Nitin Mahajan Todd E. Druley E. Anders Kolb Erin L. Crowgey Strong concordance between RNA structural and single nucleotide variants identified via next generation sequencing techniques in primary pediatric leukemia and patient-derived xenograft samples Genomics & Informatics error-corrected sequencing genomics patient derived xenograft models pediatric cancers structural variants |
| title | Strong concordance between RNA structural and single nucleotide variants identified via next generation sequencing techniques in primary pediatric leukemia and patient-derived xenograft samples |
| title_full | Strong concordance between RNA structural and single nucleotide variants identified via next generation sequencing techniques in primary pediatric leukemia and patient-derived xenograft samples |
| title_fullStr | Strong concordance between RNA structural and single nucleotide variants identified via next generation sequencing techniques in primary pediatric leukemia and patient-derived xenograft samples |
| title_full_unstemmed | Strong concordance between RNA structural and single nucleotide variants identified via next generation sequencing techniques in primary pediatric leukemia and patient-derived xenograft samples |
| title_short | Strong concordance between RNA structural and single nucleotide variants identified via next generation sequencing techniques in primary pediatric leukemia and patient-derived xenograft samples |
| title_sort | strong concordance between rna structural and single nucleotide variants identified via next generation sequencing techniques in primary pediatric leukemia and patient derived xenograft samples |
| topic | error-corrected sequencing genomics patient derived xenograft models pediatric cancers structural variants |
| url | http://genominfo.org/upload/pdf/gi-2020-18-1-e6.pdf |
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