Diagnosis of known sarcoma fusions and novel fusion partners by targeted RNA sequencing with identification of a recurrent ACTB-FOSB fusion in pseudomyogenic hemangioendothelioma Journal Article
| Authors: | Zhu, G.; Benayed, R.; Ho, C.; Mullaney, K.; Sukhadia, P.; Rios, K.; Berry, R.; Rubin, B. P.; Nafa, K.; Wang, L.; Klimstra, D. S.; Ladanyi, M.; Hameed, M. R. |
| Article Title: | Diagnosis of known sarcoma fusions and novel fusion partners by targeted RNA sequencing with identification of a recurrent ACTB-FOSB fusion in pseudomyogenic hemangioendothelioma |
| Abstract: | Integration of morphological, immunohistochemical, and molecular methods is often necessary for the precise diagnosis and optimal clinical management of sarcomas. We have validated and implemented a clinical molecular diagnostic assay, MSK- Fusion Solid, for detection of gene fusions in solid tumors, including sarcomas. Starting with RNA extracted from formalin-fixed paraffin-embedded tumor material, this targeted RNA sequencing assay utilizes anchored multiplex PCR to detect oncogenic fusion transcripts involving 62 genes known to be recurrently rearranged in solid tumors including sarcomas without prior knowledge of fusion partners. From 1/2016 to 1/2018, 192 bone and soft tissue tumors were submitted for MSK- Fusion Solid analysis and 96% (184/192) successfully passed all the pre-sequencing quality control parameters and sequencing steps. These sarcomas encompass 24 major tumor types, including 175 soft tissue tumors and 9 osteosarcomas. Ewing and Ewing-like sarcomas, rhabdomyosarcoma, and sarcoma-not otherwise specified were the three most common tumor types. Diagnostic in-frame fusion transcripts were detected in 43% of cases, including 3% (6/184) with novel fusion partners, specifically TRPS1-PLAG1, VCP-TFE3, MYLK-BRAF, FUS-TFCP2, and ACTB-FOSB, the latter in two cases of pseudomyogenic hemangioendothelioma, representing a novel observation in this sarcoma. Our experience shows that this targeted RNA sequencing assay performs in a robust and sensitive fashion on RNA extracted from most routine clinical specimens of sarcomas thereby facilitating precise diagnosis and providing opportunities for novel fusion partner discovery. © 2018, United States & Canadian Academy of Pathology. |
| Keywords: | osteosarcoma; adult; clinical article; human tissue; aged; unclassified drug; case report; myoglobin; cd34 antigen; stem cell factor receptor; sarcoma; gene rearrangement; gene fusion; protein s 100; melan a; calponin; ca 125 antigen; wt1 protein; leiomyosarcoma; rhabdomyosarcoma; synovial sarcoma; cytokeratin; cytokeratin 5; chromogranin; malignant peripheral nerve sheath tumor; soft tissue tumor; liposarcoma; rna extraction; cyclin dependent kinase 4; chorionic gonadotropin beta subunit; cd99 antigen; protein mdm2; rna sequence; synaptophysin; hemangioendothelioma; molecular diagnosis; perivascular epithelioid cell tumor; beta actin; complement component c3d receptor; transcription factor pax8; transcription factor fosb; human; male; female; priority journal; article; pseudomyogenic hemangioendothelioma; receptor type tyrosine protein phosphatase c; platelet endothelial cell adhesion molecule 1; pancytokeratin; actb fosb gene; fus tfcp2 gene; mylk braf fusion gene; trps1 plag1 gene fusion; vcp tfe3 gene fusion |
| Journal Title: | Modern Pathology |
| Volume: | 32 |
| Issue: | 5 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2019-05-01 |
| Start Page: | 609 |
| End Page: | 620 |
| Language: | English |
| DOI: | 10.1038/s41379-018-0175-7 |
| PUBMED: | 30459475 |
| PROVIDER: | scopus |
| PMCID: | PMC6486453 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 June 2019 -- Source: Scopus |
