Genetic Characterization of Pediatric Sarcomas by Targeted RNA Sequencing
| Autor: | Michael Arnold, Cecelia R. Miller, Yvonne Moyer, Matthew R. Avenarius, Ryan D. Roberts, Richard K. Wilson, Selene C. Koo, Thomas Grossman, Julie M. Gastier-Foster, Martin Hobby, Elaine R. Mardis, Ruthann Pfau |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Neuroblastoma RAS viral oncogene homolog Somatic cell Context (language use) Computational biology Biology Pathology and Forensic Medicine Fusion gene 03 medical and health sciences 0302 clinical medicine Multiplex polymerase chain reaction Humans Child Indel Gene Sequence Analysis RNA Infant Newborn Infant RNA Regular Article Sarcoma 030104 developmental biology Child Preschool 030220 oncology & carcinogenesis Molecular Medicine Female |
| Zdroj: | J Mol Diagn |
| ISSN: | 1525-1578 |
| DOI: | 10.1016/j.jmoldx.2020.07.004 |
| Popis: | Somatic variants, primarily fusion genes and single-nucleotide variants (SNVs) or insertions/deletions (indels), are prevalent among sarcomas. In many cases, accurate diagnosis of these tumors incorporates genetic findings that may also carry prognostic or therapeutic significance. Using the anchored multiplex PCR-based FusionPlex system, a custom RNA sequencing panel was developed that simultaneously detects fusion genes, SNVs, and indels in 112 genes found to be recurrently mutated in solid tumors. Using this assay, a retrospective analysis was conducted to identify somatic variants that may have assisted with classifying a cohort of 90 previously uncharacterized primarily pediatric sarcoma specimens. In total, somatic variants were identified in 45.5% (41/90) of the samples tested, including 22 cases with fusion genes and 19 cases with SNVs or indels. In addition, two of these findings represent novel alterations: a WHSC1L1/NCOA2 fusion and a novel in-frame deletion in the NRAS gene (NM_002524: c.174_176delAGC p.Ala59del). These sequencing results, taken in context with the available clinical data, indicate a potential change in the initial diagnosis, prognosis, or management in 27 of the 90 cases. This study presents a custom RNA sequencing assay that detects fusion genes and SNVs in tandem and has the ability to identify novel fusion partners. These features highlight the advantages associated with utilizing anchored multiplex PCR technology for the rapid and highly sensitive detection of somatic variants. |
| Databáze: | OpenAIRE |
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