Expanding the Spectrum of Intraosseous Rhabdomyosarcoma: Correlation Between 2 Distinct Gene Fusions and Phenotype
| العنوان: | Expanding the Spectrum of Intraosseous Rhabdomyosarcoma: Correlation Between 2 Distinct Gene Fusions and Phenotype |
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| المؤلفون: | Albert J. H. Suurmeijer, Richard Williamson, Yun-Shao Sung, Cristina R. Antonescu, David Swanson, Lei Zhang, Brendan C. Dickson, Scott Sommerville, Narasimhan P. Agaram, Dianne Torrence, Leonard H. Wexler, Glenn Francis, Marcela S. Cavalcanti |
| المساهمون: | Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| المصدر: | Am J Surg Pathol American Journal of Surgical Pathology, 43(5), 695-702. LIPPINCOTT WILLIAMS & WILKINS |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | INVOLVEMENT, 0301 basic medicine, Male, Pathology, Fusion gene, Nuclear Receptor Coactivator 2, LSF, 0302 clinical medicine, EMBRYONAL RHABDOMYOSARCOMA, Rhabdomyosarcoma, Myeloid Ecotropic Viral Integration Site 1 Protein, intraosseous, In Situ Hybridization, Fluorescence, Gene Rearrangement, medicine.diagnostic_test, TFCP2 Gene, DNA-Binding Proteins, Phenotype, EWSR1, 030220 oncology & carcinogenesis, Female, NCOA2, Anatomy, Gene Fusion, BONE, EXPRESSION, Adult, medicine.medical_specialty, Bone Neoplasms, ONCOGENE, Biology, MEIS1, Article, Pathology and Forensic Medicine, 03 medical and health sciences, Cytokeratin, Young Adult, medicine, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, FUS, IDENTIFICATION, TFCP2, Sequence Analysis, RNA, SOFT-TISSUE, Gene rearrangement, medicine.disease, 030104 developmental biology, RNA-Binding Protein FUS, Surgery, Desmin, SMALL-MOLECULE INHIBITORS, Embryonal rhabdomyosarcoma, RNA-Binding Protein EWS, Fluorescence in situ hybridization, Transcription Factors |
| الوصف: | Primary intraosseous rhabdomyosarcomas are extremely rare. Recently two studies reported 4 cases of primary intraosseous rhabdomyosarcoma with EWSR1/FUS-TFCP2 gene fusions, associated with somewhat conflicting histologic features, ranging from spindle to epithelioid. In this study we sought to further investigate the pathologic and molecular abnormalities of a larger group of intraosseous rhabdomyosarcomas by a combined approach using targeted RNA sequencing analysis and fluorescence in-situ hybridization (FISH). We identified 7 cases, 3 males and 4 females, all in young adults, age range 20–39 years (median 27 years). Three cases involved the pelvis, 2 involved the femur and 1 each involved the maxilla and the skull. Molecular studies identified recurrent gene fusions in all 7 cases tested, including: a novel MEIS1-NCOA2 fusion in 2 cases, EWSR1-TFCP2 in 3 cases and FUS-TFCP2 gene fusions in 1 case. One case showed a FUS gene rearrangement, without a TFCP2 gene abnormality by FISH. The MEIS1-NCOA2 positive cases were characterized by a more primitive and fascicular spindle cell appearance, while the EWSR1/FUS rearranged tumors had a hybrid spindle and epithelioid phenotype, with more abundant eosinophilic cytoplasm and mild nuclear pleomorphism. Immunohistochemically, all tumors were positive for desmin and myogenin (focal). In addition, 4 tumors with TFCP2 associated gene fusions also co-expressed ALK and Cytokeratin. In conclusion, our results suggest a high incidence of gene fusions in primary rhabdomyosarcomas of bone, with two molecular subsets emerging, defined by either MEIS1-NCOA2 or EWSR1/FUS-TFCP2 fusions, showing distinct morphology and immunophenotype. Additional studies with larger numbers of cases and longer follow-up data are required to definitively evaluate the biologic behavior of these tumors and to establish their relationship to other spindle cell rhabdomyosarcoma genetic groups. |
| تدمد: | 1532-0979 0147-5185 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ae2303cbebcf241309a2460ff52163acTest https://pubmed.ncbi.nlm.nih.gov/30720533Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ae2303cbebcf241309a2460ff52163ac |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15320979 01475185 |
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