-
BioRxiv : the Preprint Server For... May 2024Synovial sarcoma (SyS) is an aggressive soft-tissue malignancy characterized by a pathognomonic chromosomal translocation leading to the formation of the SS18::SSX...
Synovial sarcoma (SyS) is an aggressive soft-tissue malignancy characterized by a pathognomonic chromosomal translocation leading to the formation of the SS18::SSX fusion oncoprotein. SS18::SSX associates with mammalian BAF complexes suggesting deregulation of chromatin architecture as the oncogenic driver in this tumour type. To examine the epigenomic state of SyS we performed comprehensive multi-omics analysis on 52 primary pre-treatment human SyS tumours. Our analysis revealed a continuum of epigenomic states across the cohort at fusion target genes independent of rare somatic genetic lesions. We identify cell-of-origin signatures defined by enhancer states and reveal unexpected relationships between H2AK119Ub1 and active marks. The number of bivalent promoters, dually marked by the repressive H3K27me3 and activating H3K4me3 marks, has strong prognostic value and outperforms tumor grade in predicting patient outcome. Finally, we identify SyS defining epigenomic features including H3K4me3 expansion associated with striking promoter DNA hypomethylation in which SyS displays the lowest mean methylation level of any sarcoma subtype. We explore these distinctive features as potential vulnerabilities in SyS and identify H3K4me3 inhibition as a promising therapeutic strategy.
PubMed: 38798672
DOI: 10.1101/2024.05.14.594262 -
Diagnostics (Basel, Switzerland) May 2024Thank you for your comment; it adds value to the article and highlights the importance of molecular testing [...].
Thank you for your comment; it adds value to the article and highlights the importance of molecular testing [...].
PubMed: 38786311
DOI: 10.3390/diagnostics14101013 -
Diagnostics (Basel, Switzerland) May 2024With great interest, we read the article by Manole et al [...].
With great interest, we read the article by Manole et al [...].
PubMed: 38786310
DOI: 10.3390/diagnostics14101012 -
Bone Marrow Transplantation May 2024
False-positive human immunodeficiency virus nuclear acid amplification technique testing following therapy with transgenic T cell receptor cellular therapy for synovial sarcoma.
PubMed: 38760477
DOI: 10.1038/s41409-024-02307-1 -
Zhonghua Zhong Liu Za Zhi [Chinese... May 2024To investigate the proportion of different histological types and CT enhanced imaging features of primary middle mediastinal lesions in order to improve the...
To investigate the proportion of different histological types and CT enhanced imaging features of primary middle mediastinal lesions in order to improve the understanding of these tumors and the accuracy of preoperative diagnosis. Retrospective analysis was conducted on 84 patients with primary middle mediastinal lesions and clear histological classifications diagnosed and treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2012 to December 2022. Clinical, imaging, and pathological data were collected and classified according to tumor histological classifications. CT imaging manifestations such as tumor location, size, morphology, edge, boundary, internal components, enhancement characteristics, and surrounding tissue invasion were evaluated and recorded. The histological types of the primary middle mediastinal lesions from the 84 patients included mesenchymal tumors, anterior intestinal cysts, giant lymph node hyperplasia, substernal goiter, neuroendocrine carcinoma, lymphohematopoietic system tumors, and mesothelioma, accounting for 28.6%, 27.4%, 14.3%, 3.6%, 11.9%, 9.5%, and 4.8%, respectively. Mesenchymal tumors included peripheral nerve sheath tumors, vascular tumors, adipogenic tumors, solitary fibrous tumors, and synovial sarcoma, accounting for 54.2%, 20.8%, 12.5%, 8.3%, and 4.2%, respectively. The above tumors had diverse imaging manifestations and specific imaging features. Mature fat were found in 3 cases of liposarcoma; Calcification was observed in 2 cases of thyroid nodules and 7 cases of giant lymph node hyperplasia; Enhanced scanning showed significant enhancement in 2 cases of solitary fibrous tumors, 3 cases of thyroid nodules, and 11 cases of giant lymph node hyperplasia; Mediastinal large lymph nodes was observed in 6 cases of lymphoma and 3 cases of mesothelioma; High invasiveness was observed in 4 cases of mesothelioma and 9 cases of neuroendocrine carcinoma. Mediastinal tumors have low incidence rate and rich histological types, and their imaging manifestations are diverse. Preoperative differential diagnosis can be made according to their specific imaging characteristics.
Topics: Humans; Mediastinal Neoplasms; Retrospective Studies; Tomography, X-Ray Computed; Carcinoma, Neuroendocrine; Lymph Nodes; Mediastinum; Sarcoma, Synovial; Middle Aged; Male; Female
PubMed: 38742358
DOI: 10.3760/cma.j.cn112152-20230903-00114 -
Maedica Mar 2024Malignant solitary fibrous tumor of the breast is one of the rarest types of breast malignancy. To the best of our knowledge, only six cases have been reported so far....
Malignant solitary fibrous tumor of the breast is one of the rarest types of breast malignancy. To the best of our knowledge, only six cases have been reported so far. Here we have presented such a case from India, where a 52-year-old lady presented with a 10 cm x 8 cm breast lump. Diagnosis was achieved with the help of FDG PET, histopathology and immunohistochemistry, which showed nuclear positivity for STAT6. Fluorescent in situ hybridization (FISH) molecular study for SS18-SSX was used to rule out the differential diagnosis of synovial sarcoma. Guidelines for the management of this type of breast malignancy still do not exist. We have done a review of the literature in order to discuss which might be the best management in such cases. Evidence on this very rarest type of breast malignancy is still evolving. The interest in the case described here relies on its rarity, difficulties in achieving diagnosis and formulation of the proper management.
PubMed: 38736930
DOI: 10.26574/maedica.2024.19.11.170 -
Skeletal Radiology May 2024Synovial sarcoma (SS) is a malignant tumor comprising 5-10% of all soft tissue sarcomas. SS has distinct characteristics, such as a predilection for young adults and...
Synovial sarcoma (SS) is a malignant tumor comprising 5-10% of all soft tissue sarcomas. SS has distinct characteristics, such as a predilection for young adults and relatively slow growth compared to other soft tissue sarcomas. Some patients with SS experience long-standing pain at the tumor site before the development of a palpable mass. Herein, we report the case of a 39-year-old woman with SS in the upper arm who presented with pain for > 20 years. The tumor detected on magnetic resonance imaging at 17 years was an SS. To the best of our knowledge, no English-language reports on imaging study-based identification of SS, which was undiagnosed for > 20 years, are known in the literature. This report discusses the imaging features of this latent lesion and the volume-doubling time of this unusual tumor.
PubMed: 38727739
DOI: 10.1007/s00256-024-04701-8 -
Current Opinion in Oncology Jul 2024There are numerous sarcoma subtypes and vary widely in terms of epidemiology, clinical characteristics, genetic profiles, and pathophysiology. They also differ widely... (Review)
Review
PURPOSE OF REVIEW
There are numerous sarcoma subtypes and vary widely in terms of epidemiology, clinical characteristics, genetic profiles, and pathophysiology. They also differ widely between ethnic groups. This review focuses on the different incidence rates of sarcomas in different regions and the potential explanations for these disparities.
RECENT FINDINGS
In an intercontinental study using national cancer registry databases from France and Taiwan, the French population had a higher risk of liposarcomas, leiomyosarcomas, and synovial sarcomas, whereas the Taiwanese population had a higher incidence of angiosarcomas and malignant peripheral nerve sheath tumors. The anatomical distribution of these sarcomas also varied between these two regions. In France, most angiosarcoma cases occurred in the extremities and trunk, whereas in Taiwan, angiosarcoma cases in the abdomen and pelvis were more common. Another international study showed that in addition to the common known TP53 and NF1 germline mutations, genes involved in centromere and telomere maintenance were also involved in sarcomagenesis. We reviewed factors related to genetics, environmental effects, chemical exposure, and radiation exposure that could explain the differences in sarcoma incidence among different geographical or ethnic regions.
SUMMARY
Our understanding of the potential cause of sarcomas with different subtypes is limited. Establishing a comprehensive global database for patients with sarcomas from all ethnic groups is essential to deepen our understanding of the potential risk factors and the pathophysiology of all sarcoma subtypes.
Topics: Humans; Global Health; Incidence; Sarcoma; Taiwan; France
PubMed: 38726812
DOI: 10.1097/CCO.0000000000001046 -
Asian Journal of Surgery May 2024
PubMed: 38724380
DOI: 10.1016/j.asjsur.2024.05.022 -
BioRxiv : the Preprint Server For... Apr 2024Synovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein. and is ultimately refractory to therapeutic approaches. SS18::SSX alters ATP-dependent chromatin...
Synovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein. and is ultimately refractory to therapeutic approaches. SS18::SSX alters ATP-dependent chromatin remodeling BAF (mammalian SWI/SNF) complexes, leading to the degradation of canonical (cBAF) complex and amplified presence of an SS18::SSX-containing non-canonical BAF (ncBAF or GBAF) that drives an SS-specific transcription program and tumorigenesis. We demonstrate that SS18::SSX activates the SUMOylation program and SSs are sensitive to the small molecule SAE1/2 inhibitor, TAK-981. Mechanistically, TAK-981 de-SUMOylates the cBAF subunit SMARCE1, stabilizing and restoring cBAF on chromatin, shifting away from SS18::SSX-ncBAF-driven transcription, associated with DNA damage and cell death and resulting in tumor inhibition across both human and mouse SS tumor models. TAK-981 synergized with cytotoxic chemotherapy through increased DNA damage, leading to tumor regression. Targeting the SUMOylation pathway in SS restores cBAF complexes and blocks the SS18::SSX-ncBAF transcriptome, identifying a therapeutic vulnerability in SS, positioning the in-clinic TAK-981 to treat SS.
PubMed: 38712286
DOI: 10.1101/2024.04.25.591023