scispace - formally typeset
Search or ask a question
Author

Jerry Hussong

Bio: Jerry Hussong is an academic researcher. The author has contributed to research in topics: Angiomatoid fibrous histiocytoma. The author has an hindex of 1, co-authored 1 publications receiving 74 citations.

Papers
More filters
Journal ArticleDOI
TL;DR: The first pathologically confirmed case of an AFH presenting as an intracerebral primary in a previously healthy 25-year-old man is reported, and genetic analyses revealed a t(12;22)(q13;q12) and a unique underlying clear cell sarcomalike type 1 EWS/ATF-1 gene fusion.
Abstract: Angiomatoid fibrous histiocytoma (AFH) is generally considered a soft tissue sarcoma of low malignant potential that occurs in children/young adults and most frequently affects the extremities. AFH infrequently recurs and rarely metastasizes. AFH has a characteristic histomorphology, and immunohistochemical reactivities for desmin and CD68 have led to myofibroblastic and fibrohistiocytic histogenetic hypotheses, respectively. Although only a limited number of AFH cases have been molecularly characterized, many have demonstrated evidence of an underlying translocation event. Reverse transcription-polymerase chain reaction and fluorescence in situ hybridization studies suggest that chromosomal rearrangement in AFH most frequently involve the EWS, CREB, ATF-1, and FUS genes. We report the first pathologically confirmed case of an AFH presenting as an intracerebral primary in a previously healthy 25-year-old man. Genetic analyses revealed a t(12;22)(q13;q12) and a unique underlying clear cell sarcomalike type 1 EWS/ATF-1 gene fusion.

85 citations


Cited by
More filters
Journal ArticleDOI
TL;DR: Altered genes in BRAF, FGFR1, or MYB account for most pathogenic alterations in LGNTs, including pilocytic astrocytomas, and alignment of these genetic alterations and cytologic features acrossLGNTs has diagnostic implications.
Abstract: Low-grade neuroepithelial tumors (LGNTs) are diverse CNS tumors presenting in children and young adults, often with a history of epilepsy. While the genetic profiles of common LGNTs, such as the pilocytic astrocytoma and ‘adult-type’ diffuse gliomas, are largely established, those of uncommon LGNTs remain to be defined. In this study, we have used massively parallel sequencing and various targeted molecular genetic approaches to study alterations in 91 LGNTs, mostly from children but including young adult patients. These tumors comprise dysembryoplastic neuroepithelial tumors (DNETs; n = 22), diffuse oligodendroglial tumors (d-OTs; n = 20), diffuse astrocytomas (DAs; n = 17), angiocentric gliomas (n = 15), and gangliogliomas (n = 17). Most LGNTs (84 %) analyzed by whole-genome sequencing (WGS) were characterized by a single driver genetic alteration. Alterations of FGFR1 occurred frequently in LGNTs composed of oligodendrocyte-like cells, being present in 82 % of DNETs and 40 % of d-OTs. In contrast, a MYB-QKI fusion characterized almost all angiocentric gliomas (87 %), and MYB fusion genes were the most common genetic alteration in DAs (41 %). A BRAF:p.V600E mutation was present in 35 % of gangliogliomas and 18 % of DAs. Pathogenic alterations in FGFR1/2/3, BRAF, or MYB/MYBL1 occurred in 78 % of the series. Adult-type d-OTs with an IDH1/2 mutation occurred in four adolescents, the youngest aged 15 years at biopsy. Despite a detailed analysis, novel genetic alterations were limited to two fusion genes, EWSR1-PATZ1 and SLMAP-NTRK2, both in gangliogliomas. Alterations in BRAF, FGFR1, or MYB account for most pathogenic alterations in LGNTs, including pilocytic astrocytomas, and alignment of these genetic alterations and cytologic features across LGNTs has diagnostic implications. Additionally, therapeutic options based upon targeting the effects of these alterations are already in clinical trials.

269 citations

Journal ArticleDOI
TL;DR: A review of the clinicopathologic and molecular features of this group of neoplasms unified by the presence of EWSR1-CREB1 and EWSR-ATF1 genetic fusions, which have now been consistently described in 5 histopathologically and behaviorally diverse neoplasm.
Abstract: EWSR1-CREB1 and EWSR1-ATF1 are gene fusions of which one or both have now been consistently described in 5 histopathologically and behaviorally diverse neoplasms: angiomatoid fibrous histiocytoma, conventional clear cell sarcoma (of tendons and aponeuroses), clear cell sarcoma-like tumor of the gastrointestinal tract, hyalinizing clear cell carcinoma of the salivary gland, and primary pulmonary myxoid sarcoma. Some of the tumors in this group have been described only recently, and others have been the subject of recent genetic insights contributing to their characterization. These neoplasms are all rare; yet, the increasing frequency with which EWSR1-CREB1 and EWSR1-ATF1 fusions are being described in separate entities is noteworthy. The additional molecular mechanisms by which tumors with such variable morphologic, immunohistochemical, and clinical phenotypes are generated are yet to be understood. We review the clinicopathologic and molecular features of this group of neoplasms unified by the presence of EWSR1-CREB1 and EWSR1-ATF1 genetic fusions.

201 citations

Journal ArticleDOI
TL;DR: The results show that ATF-1 mediates HO-1 induction by heme and drives macrophage adaptation to intraplaque hemorrhage, and the definition of anATF-1–mediated pathway for linked protection from foam cell formation and oxidant stress may have therapeutic potential.
Abstract: Rationale: Intraplaque hemorrhage (IPH) drives atherosclerosis through the dual metabolic stresses of cholesterol-enriched erythrocyte membranes and pro-oxidant heme/iron. When clearing tissue hemorrhage, macrophages are typically seen storing either iron or lipid. We have recently defined hemorrhage-associated macrophages (HA-mac) as a plaque macrophage population that responds adaptively to IPH. Objective: This study aimed to define the key transcription factor(s) involved in HO-1 induction by heme. Methods and Results: To address this question, we used microarray analysis and transfection with siRNA and plasmids. To maintain physiological relevance, we focused on human blood-derived monocytes. We found that heme stimulates monocytes through induction of activating transcription factor 1 (ATF-1). ATF-1 coinduces heme oxygenase-1 (HO-1) and Liver X receptor beta (LXR-β). Heme-induced HO-1 and LXR-β were suppressed by knockdown of ATF-1, and HO-1 and LXR-β were induced by ATF-1 transfection. ATF-1 required phosphorylation for full functional activity. Expression of LXR-β in turn led to induction of other genes central to cholesterol efflux, such as LXR-α and ABCA1. This heme-directed state was distinct from known macrophage states (M1, M2, Mox) and, following the same format, we have designated them Mhem. Conclusions: These results show that ATF-1 mediates HO-1 induction by heme and drives macrophage adaptation to intraplaque hemorrhage. Our definition of an ATF-1–mediated pathway for linked protection from foam cell formation and oxidant stress may have therapeutic potential.

170 citations

Journal ArticleDOI
TL;DR: The diversity of the several soft tissue tumour types that are associated with rearrangement of the EWSR1 gene is reviewed.
Abstract: Many soft tissue sarcomas have chromosomal translocations with resultant formation of new fusion genes. Among the genes that can be rearranged, the EWSR1 gene has been identified as a partner in a wide variety of clinically and pathologically diverse sarcomas as well as some non-mesenchymal tumours. The former include Ewing sarcoma and similar (Ewing-like) small round cell sarcomas, desmoplastic small round cell tumour, myxoid liposarcoma, extraskeletal myxoid chondrosarcoma, angiomatoid fibrous histiocytoma, clear cell sarcoma of soft tissue and clear cell sarcoma-like tumours of the gastrointestinal tract, primary pulmonary myxoid sarcoma, extrasalivary myoepithelial tumours and sporadic examples of low-grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma and mesothelioma. EWSR1 is a 'promiscuous' gene that can fuse with many different partner genes, but sometimes this results in phenotypically identical tumours. EWSR1 can, conversely, partner with the same genes in morphologically and behaviourally different neoplasms. This paper reviews the diversity of the several soft tissue tumour types that are associated with rearrangement of the EWSR1 gene.

145 citations

Journal ArticleDOI
TL;DR: Comparison of the reported cases of extrasomatic angiomatoid fibrous histiocytoma with their somatic soft tissue counterparts showed a number of differences: higher mean age, slight male predominance (particularly for bone lesions), larger tumors, higher frequency of systemic symptoms, higher recurrence rate, myxoid change being more common and a muchHigher frequency of EWS/ATF1 gene fusion.

125 citations