| Autor: |
Schieffer KM; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43215, USA.; Department of Pathology, The Ohio State University, Columbus, OH 43210, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH 43210, USA., Moccia A; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43215, USA., Bucknor BA; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43215, USA., Stonerock E; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43215, USA., Jayaraman V; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43215, USA., Jenkins H; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43215, USA., McKinney A; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43215, USA., Koo SC; Department of Pathology, The Ohio State University, Columbus, OH 43210, USA.; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH 43205, USA., Mathew MT; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43215, USA.; Department of Pathology, The Ohio State University, Columbus, OH 43210, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH 43210, USA., Mardis ER; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43215, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH 43210, USA., Lee K; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43215, USA.; Department of Pathology, The Ohio State University, Columbus, OH 43210, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH 43210, USA., Reshmi SC; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43215, USA.; Department of Pathology, The Ohio State University, Columbus, OH 43210, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH 43210, USA., Cottrell CE; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43215, USA.; Department of Pathology, The Ohio State University, Columbus, OH 43210, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH 43210, USA. |
| Abstrakt: |
Gene fusions are a form of structural rearrangement well established as driver events in pediatric and adult cancers. The identification of such events holds clinical significance in the refinement, prognostication, and provision of treatment in cancer. Structural rearrangements also extend beyond fusions to include intragenic rearrangements, such as internal tandem duplications (ITDs) or exon-level deletions. These intragenic events have been increasingly implicated as cancer-promoting events. However, the detection of intragenic rearrangements may be challenging to resolve bioinformatically with short-read sequencing technologies and therefore may not be routinely assessed in panel-based testing. Within an academic clinical laboratory, over three years, a total of 608 disease-involved samples (522 hematologic malignancy, 86 solid tumors) underwent clinical testing using Anchored Multiplex PCR (AMP)-based RNA sequencing. Hematologic malignancies were evaluated using a custom Pan-Heme 154 gene panel, while solid tumors were assessed using a custom Pan-Solid 115 gene panel. Gene fusions, ITDs, and intragenic deletions were assessed for diagnostic, prognostic, or therapeutic significance. When considering gene fusions alone, we report an overall diagnostic yield of 36% (37% hematologic malignancy, 41% solid tumors). When including intragenic structural rearrangements, the overall diagnostic yield increased to 48% (48% hematologic malignancy, 45% solid tumor). We demonstrate the clinical utility of reporting structural rearrangements, including gene fusions and intragenic structural rearrangements, using an AMP-based RNA sequencing panel. |
