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Christopher D M Fletcher - One of the best experts on this subject based on the ideXlab platform.
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a novel nfix stat6 gene fusion in Solitary Fibrous Tumor a case report
International Journal of Molecular Sciences, 2021Co-Authors: David S Moura, Juan Diazmartin, Silvia Bague, Ruth Orellanafernandez, Ana Sebio, Jose L Mondazahernandez, Carmen Salgueroaranda, Federico Rojo, Nadia Hindi, Christopher D M FletcherAbstract:Solitary Fibrous Tumor is a rare subtype of soft-tissue sarcoma with a wide spectrum of histopathological features and clinical behaviors, ranging from mildly to highly aggressive Tumors. The defining genetic driver alteration is the gene fusion NAB2–STAT6, resulting from a paracentric inversion within chromosome 12q, and involving several different exons in each gene. STAT6 (signal transducer and activator of transcription 6) nuclear immunostaining and/or the identification of NAB2–STAT6 gene fusion is required for the diagnostic confirmation of Solitary Fibrous Tumor. In the present study, a new gene fusion consisting of Nuclear Factor I X (NFIX), mapping to 19p13.2 and STAT6, mapping to 12q13.3 was identified by targeted RNA-Seq in a 74-year-old female patient diagnosed with a deep-seated Solitary Fibrous Tumor in the pelvis. Histopathologically, the neoplasm did not display nuclear pleomorphism or Tumor necrosis and had a low proliferative index. A total of 378 unique reads spanning the NFIXexon8–STAT6exon2 breakpoint with 55 different start sites were detected in the bioinformatic analysis, which represented 59.5% of the reads intersecting the genomic location on either side of the breakpoint. Targeted RNA-Seq results were validated by RT-PCR/ Sanger sequencing. The identification of a new gene fusion partner for STAT6 in Solitary Fibrous Tumor opens intriguing new hypotheses to refine the role of STAT6 in the sarcomatogenesis of this entity.
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tert promoter mutations and prognosis in Solitary Fibrous Tumor
Modern Pathology, 2016Co-Authors: Armita Bahrami, Seungjae Lee, Ingamarie Schaefer, Jennifer M Boland, Kurt T Patton, Stanley Pounds, Christopher D M FletcherAbstract:Solitary Fibrous Tumor is a mesenchymal neoplasm exhibiting a broad spectrum of biological behavior and harboring the NAB2-STAT6 fusion. Clinicopathologic parameters are currently used in risk-prediction models for Solitary Fibrous Tumor, but the molecular determinants of malignancy in Solitary Fibrous Tumors remain unknown. We proposed that the activation of telomere maintenance pathways confers a perpetual malignant phenotype to these Tumors. Therefore, we investigated telomerase reverse transcriptase (TERT) reactivation induced by promoter mutations as a potential molecular mechanism for aggressive clinical behavior in Solitary Fibrous Tumor. The retrospective study included Tumor samples from 94 patients with Solitary Fibrous Tumor (31 thoracic and 63 extra-thoracic). Follow-up information was available for 68 patients (median, 46 months). TERT promoter mutation analysis was performed by PCR and Sanger sequencing, and TERT mRNA expression was assessed by real-time quantitative reverse transcription PCR. Patients were stratified into clinicopathologic subgroups (high-risk (n=20), moderate-risk (n=28), and low-risk (n=46)) according to the risk-stratification model proposed by Demicco et al. TERT promoter mutations were identified in 26 of 94 (28%) Solitary Fibrous Tumors: -124C>T in 23 Tumors (88%), -124C>A in 1 Tumor (4%), and -146C>T in 2 Tumors (8%). Real-time quantitative reverse transcription PCR revealed that TERT mRNA expression was higher in all Solitary Fibrous Tumors with the mutant TERT promoter than those with the wild-type TERT promoter. TERT promoter mutations were strongly associated with high-risk clinicopathologic characteristics and outcome. An adverse event (relapse, death) occurred in 16 of 68 (24%) patients, 12 with Solitary Fibrous Tumors with TERT promoter mutations and 4 with the wild-type TERT promoter. TERT promoter mutations were strongly associated with older age (P=0.006), larger Tumor size (P=0.000002), higher risk classifications (P=2.9 × 10-9), and a worse event-free survival (P=0.0082). Thus, TERT promoter mutations in Solitary Fibrous Tumor influence gene expression and are associated with adverse patient outcome. Integrating TERT promoter mutational status with existing multivariable risk-prediction models might improve risk prediction in patients with Solitary Fibrous Tumor.
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malignant giant Solitary Fibrous Tumor of the mediastinum
Journal of Thoracic Oncology, 2008Co-Authors: Jan De Raet, Christopher D M Fletcher, Robert Sacre, Anne Hoorens, Jan LamoteAbstract:Malignant giant Solitary Fibrous Tumor (SFT) of the mediastinum is a rare neoplasm derived from mesenchymal tissue. Owing to its large size, a complete resection of the Tumor can present many challenges, particularly given its proximity to vital neighboring structures. We report a successful en-bloc resection of a massive mediastinal SFT, which was compressing the inferior trachea and heart, by means of a median sternotomy and an anterior left thoracotomy. We emphasize the rarity of this uncommon mediastinal mass. Key points of mediastinal SFT are discussed.
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Solitary Fibrous Tumor of the orbit
International Journal of Surgical Pathology, 1995Co-Authors: David R Lucas, Christopher D M Fletcher, Jean R Campbell, James A Garrity, Antonio G Nascimento, Alison C E MccartneyAbstract:We report three cases of Solitary Fibrous Tumor (SFT) arising in the orbit. All patients presented with nontender swelling of the affected eye, and one patient presented with nasolacrimal duct obstruction. All three patients had well-circumscribed Tumors that had histologic features identical to those of SFT of the pleura (Fibrous mesothelioma). The neoplastic cells were purely fibrogenic. They were reactive with antivimentin and CD-34 and demonstrated no smooth muscle or neural differentiation (nonreactive with antibodies to actin, desmin, and S 100 protein). KP-1 (CD-68) immunoreactivity was present focally within the neoplastic cells in all three Tumors; however, it was strongly positive within Tumor infiltrating macrophages. Electron microscopy per formed on one Tumor showed fine fibroblastic differentiation with phagocytic activity confined to infiltrating macrophages. SFT of the orbit is a distinct pathologic entity that merits distinction within the broad group of orbital Fibrous Tumors. Int J Surg...
John A Jane - One of the best experts on this subject based on the ideXlab platform.
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Solitary Fibrous Tumor of the spinal cord
The American Journal of Surgical Pathology, 1997Co-Authors: S R Alston, Paul C Francel, John A JaneAbstract:We report a case of primary Solitary Fibrous Tumor occurring in the intramedullary thoracic spinal cord in a 47-year-old man. The Tumor predominately consisted of spindle cells separated by abundant collagen; a few areas of hemangiopericytomatous morphology were also present. The diagnosis was confirmed by immunohistochemistry and electron microscopy. The Tumor was reactive to vimentin and CD34 but was negative for glial fibrillary acid protein (GFAP), S-100, smooth muscle actin, epithelial membrane antigen, HMB-45, myelin basic protein, and keratin; ultrastructural examination showed fairly undifferentiated cells within a collagenous matrix, few tight junctions, and sparse extravascular basement membrane. The occurrence of this Tumor within the spinal cord parenchyma and in other extraserosal sites emphasizes the current belief that Solitary Fibrous Tumors arise from mesenchymal tissues and are not restricted to the pleura and other serosal surfaces. Furthermore, Solitary Fibrous Tumor is an entity that must be considered in the differential diagnosis of spindle cell central nervous system neoplasms.
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Solitary Fibrous Tumor of the spinal cord
The American Journal of Surgical Pathology, 1997Co-Authors: S R Alston, Paul C Francel, John A JaneAbstract:We report a case of primary Solitary Fibrous Tumor occurring in the intramedullary thoracic spinal cord in a 47-year-old man. The Tumor predominately consisted of spindle cells separated by abundant collagen; a few areas of hemangiopericytomatous morphology were also present. The diagnosis was co
S R Alston - One of the best experts on this subject based on the ideXlab platform.
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Solitary Fibrous Tumor of the spinal cord
The American Journal of Surgical Pathology, 1997Co-Authors: S R Alston, Paul C Francel, John A JaneAbstract:We report a case of primary Solitary Fibrous Tumor occurring in the intramedullary thoracic spinal cord in a 47-year-old man. The Tumor predominately consisted of spindle cells separated by abundant collagen; a few areas of hemangiopericytomatous morphology were also present. The diagnosis was confirmed by immunohistochemistry and electron microscopy. The Tumor was reactive to vimentin and CD34 but was negative for glial fibrillary acid protein (GFAP), S-100, smooth muscle actin, epithelial membrane antigen, HMB-45, myelin basic protein, and keratin; ultrastructural examination showed fairly undifferentiated cells within a collagenous matrix, few tight junctions, and sparse extravascular basement membrane. The occurrence of this Tumor within the spinal cord parenchyma and in other extraserosal sites emphasizes the current belief that Solitary Fibrous Tumors arise from mesenchymal tissues and are not restricted to the pleura and other serosal surfaces. Furthermore, Solitary Fibrous Tumor is an entity that must be considered in the differential diagnosis of spindle cell central nervous system neoplasms.
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Solitary Fibrous Tumor of the spinal cord
The American Journal of Surgical Pathology, 1997Co-Authors: S R Alston, Paul C Francel, John A JaneAbstract:We report a case of primary Solitary Fibrous Tumor occurring in the intramedullary thoracic spinal cord in a 47-year-old man. The Tumor predominately consisted of spindle cells separated by abundant collagen; a few areas of hemangiopericytomatous morphology were also present. The diagnosis was co
David S Moura - One of the best experts on this subject based on the ideXlab platform.
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a novel nfix stat6 gene fusion in Solitary Fibrous Tumor a case report
International Journal of Molecular Sciences, 2021Co-Authors: David S Moura, Juan Diazmartin, Silvia Bague, Ruth Orellanafernandez, Ana Sebio, Jose L Mondazahernandez, Carmen Salgueroaranda, Federico Rojo, Nadia Hindi, Christopher D M FletcherAbstract:Solitary Fibrous Tumor is a rare subtype of soft-tissue sarcoma with a wide spectrum of histopathological features and clinical behaviors, ranging from mildly to highly aggressive Tumors. The defining genetic driver alteration is the gene fusion NAB2–STAT6, resulting from a paracentric inversion within chromosome 12q, and involving several different exons in each gene. STAT6 (signal transducer and activator of transcription 6) nuclear immunostaining and/or the identification of NAB2–STAT6 gene fusion is required for the diagnostic confirmation of Solitary Fibrous Tumor. In the present study, a new gene fusion consisting of Nuclear Factor I X (NFIX), mapping to 19p13.2 and STAT6, mapping to 12q13.3 was identified by targeted RNA-Seq in a 74-year-old female patient diagnosed with a deep-seated Solitary Fibrous Tumor in the pelvis. Histopathologically, the neoplasm did not display nuclear pleomorphism or Tumor necrosis and had a low proliferative index. A total of 378 unique reads spanning the NFIXexon8–STAT6exon2 breakpoint with 55 different start sites were detected in the bioinformatic analysis, which represented 59.5% of the reads intersecting the genomic location on either side of the breakpoint. Targeted RNA-Seq results were validated by RT-PCR/ Sanger sequencing. The identification of a new gene fusion partner for STAT6 in Solitary Fibrous Tumor opens intriguing new hypotheses to refine the role of STAT6 in the sarcomatogenesis of this entity.
Dejka M Araujo - One of the best experts on this subject based on the ideXlab platform.
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new insights into the hemangiopericytoma Solitary Fibrous Tumor spectrum of Tumors
Current Opinion in Oncology, 2009Co-Authors: Min S Park, Dejka M AraujoAbstract:Purpose of reviewThis review provides an overview of the hemangiopericytoma/Solitary Fibrous Tumor (HPC/SFT) spectrum of Tumors, focusing on the histopathologic characteristics, clinical features, diagnosis, and treatment of HPC/SFT.Recent findingsDue to the relatively insensitive nature of HPC/SFT
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combination therapy with temozolomide and bevacizumab in the treatment of hemangiopericytoma malignant Solitary Fibrous Tumor
Journal of Clinical Oncology, 2008Co-Authors: Min S Park, Shabnum Patel, Joseph A Ludwig, J C Trent, Charles A Conrad, A J Lazar, Haesun Choi, Robert S Benjamin, Dejka M AraujoAbstract:10512 Background: Tumors comprising the histologic spectrum of hemangiopericytoma (HPC)/Solitary Fibrous Tumor (SFT) are rare with poor prognosis in the metastatic setting and little is known about...
