Meningioma transcriptomic landscape demonstrates novel subtypes with regional associated biology and patient outcome

Cell Genomics, Journal Year: 2024, Volume and Issue: 4(6), P. 100566 - 100566

Published: May 23, 2024

Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, better characterizations their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape 1,298 meningiomas. The clinical genomic metadata effectively correlated with regions, which led identification meningioma subtypes specific biological signatures. time recurrence also map location. Further, developed an algorithm that maps new patients onto landscape, where nearest neighbors predict outcome. This study highlights utility combining transcriptomic visualize complexity populations. provide interactive tool for understanding disease predicting patient outcomes. resource is accessible via online Oncoscape, scientific community explore landscape.

Language: Английский

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Emerging regulatory mechanisms and functions of biomolecular condensates: implications for therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 6, 2025

Cells orchestrate their processes through complex interactions, precisely organizing biomolecules in space and time. Recent discoveries have highlighted the crucial role of biomolecular condensates-membrane-less assemblies formed condensation proteins, nucleic acids, other molecules-in driving efficient dynamic cellular processes. These condensates are integral to various physiological functions, such as gene expression intracellular signal transduction, enabling rapid finely tuned responses. Their ability regulate signaling pathways is particularly significant, it requires a careful balance between flexibility precision. Disruption this can lead pathological conditions, including neurodegenerative diseases, cancer, viral infections. Consequently, emerged promising therapeutic targets, with potential offer novel approaches disease treatment. In review, we present recent insights into regulatory mechanisms by which influence pathways, roles health disease, strategies for modulating condensate dynamics approach. Understanding these emerging principles may provide valuable directions developing effective treatments targeting aberrant behavior diseases.

Language: Английский

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TEAD1::NCOA2 fusion driver in primary central nervous system malignancy: case report

Acta Neuropathologica, Journal Year: 2025, Volume and Issue: 149(1)

Published: Feb. 7, 2025

Language: Английский

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YAP1-TFE3-fused hemangioendothelioma: a multi-institutional clinicopathologic study of 24 genetically-confirmed cases

Modern Pathology, Journal Year: 2021, Volume and Issue: 34(12), P. 2211 - 2221

Published: Aug. 11, 2021

Language: Английский

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Gene fusions in poroma, porocarcinoma and related adnexal skin tumours: An update

Histopathology, Journal Year: 2023, Volume and Issue: 84(2), P. 266 - 278

Published: Aug. 23, 2023

Poroma is a benign sweat gland tumour showing morphological features recapitulating the superficial portion of eccrine coil. A subset poromas may transform into porocarcinoma, its malignant counterpart. and porocarcinoma are characterised by recurrent gene fusions involving YAP1 , transcriptional co‐activator, which controlled Hippo signalling pathway. The fusion genes frequently involve MAML2 NUTM1 also rearranged in other cutaneous extracutaneous neoplasms. We aimed to review clinical, molecular this category adnexal neoplasms with special focus upon emerging differential diagnoses, discuss how their systematic characterisation contribute standardisation diagnosis, more accurate classification and, ultimately, refinement prognosis therapeutic modalities.

Language: Английский

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Porocarcinomas with PAK1/2/3 fusions: a series of 12 cases

Histopathology, Journal Year: 2024, Volume and Issue: 85(4), P. 566 - 578

Published: May 24, 2024

Aims Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of duct and may arise from transformation preexisting benign poroma. In 2019, Sekine et al. demonstrated presence YAP1::MAML2 YAP1::NUTM1 fusions in most poromas porocarcinomas. Recently, our group identified PAK2‐ subset poromas. Herein we report series 12 porocarcinoma cases harbouring PAK1/2/3 fusions. Methods Results Five patients were male median age was 79 years (ranges: 59–95). Tumours located on trunk ( n = 7), thigh 3), neck 1), or groin area 1). Four developed distant metastases. Microscopically, seven harboured poroma component invasive part. Ductal formations observed all, while infundibular/horn cysts cells with vacuolated cytoplasm detected six tumours, respectively. three cases, consisted proliferation elongated cells, some which formed pseudovascular spaces, whereas others predominant solid trabecular growth pattern. Immunohistochemical staining for CEA EMA confirmed ducts. Focal androgen receptor expression specimens. Whole RNA sequencing evidenced LAMTOR1::PAK1 2), ZDHHC5::PAK1 DLG1::PAK2 , CTDSP1::PAK1 CTNND1::PAK1 SSR1::PAK3 CTNNA1::PAK2 RNF13::PAK2 ROBO1::PAK2, CD47::PAK2 . Activating mutation HRAS (G13V, 3, G13R, 1, Q61L, 2) present cases. Conclusion Our study suggests that oncogenic driver porocarcinomas lacking YAP1 rearrangement.

Language: Английский

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Biomolecular condensates: hubs of Hippo-YAP/TAZ signaling in cancer

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: 34(7), P. 566 - 577

Published: May 27, 2024

Language: Английский

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Molecular Classification and Therapeutic Targets in Ependymoma

Cancers, Journal Year: 2021, Volume and Issue: 13(24), P. 6218 - 6218

Published: Dec. 10, 2021

Ependymoma is a biologically diverse tumor wherein molecular classification has superseded traditional histological grading based on its superior ability to characterize behavior, prognosis, and possible targeted therapies. The current, updated of ependymoma consists ten distinct subgroups spread evenly among the spinal, infratentorial, supratentorial compartments, each with own clinical characteristics. In this review, history, histopathology, standard care, oncogenic drivers, hypothesized targets for all are explored. This review emphasizes that despite varied behavior subgroups, it remains clear research must be performed further elucidate these tumors. Although not oncologically aggressive, development therapies essential, particularly cases where surgical resection an option without causing significant morbidity. rely building upon our current understanding oncogenesis, as well cultivating transfer knowledge malignancies similar genomic alterations.

Language: Английский

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YAP–VGLL4 antagonism defines the major physiological function of the Hippo signaling effector YAP

Genes & Development, Journal Year: 2022, Volume and Issue: 36(21-24), P. 1119 - 1128

Published: Nov. 1, 2022

The Hippo–YAP signaling pathway plays a critical role in development, homeostasis, regeneration, and tumorigenesis by converging on YAP, coactivator for the TEAD family DNA-binding transcription factors, to regulate downstream programs. Given its pivotal as nuclear effector of Hippo pathway, YAP is indispensable multiple developmental tissue contexts. Here we report that essentiality liver lung development can be genetically bypassed simultaneous inactivation corepressor VGLL4. This striking antagonistic epistasis suggests major physiological function antagonize We further show YAP–VGLL4 antagonism widespread regulating output beyond normal Vgll4 dramatically enhanced intrahepatic cholangiocarcinoma formation Nf2 -deficient livers ameliorated CCl 4 -induced damage livers. Interestingly, expression temporally regulated regeneration and, certain contexts, provides better indication overall than phosphorylation. Together, these findings highlight central importance VGLL4-mediated transcriptional repression regulation inform potential strategies modulate cancer regenerative medicine.

Language: Английский

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Recurrent Fusion of the Genes for High-mobility Group AT-hook 2 (HMGA2) and Nuclear Receptor Co-repressor 2 (NCOR2) in Osteoclastic Giant Cell-rich Tumors of Bone

Cancer Genomics & Proteomics, Journal Year: 2022, Volume and Issue: 19(2), P. 163 - 177

Published: Jan. 1, 2022

Chimeras involving the high-mobility group AT-hook 2 gene (HMGA2 in 12q14.3) have been found lipomas and other benign mesenchymal tumors. We report here a fusion of HMGA2 with nuclear receptor co-repressor (NCOR2 12q24.31) repeatedly tumors bone first cytogenetic investigation this fusion.Six osteoclastic giant cell-rich were investigated using G-banding, RNA sequencing, reverse transcription polymerase chain reaction, Sanger fluorescence situ hybridization.Four had structural chromosomal aberrations 12q. The pathogenic variant c.103_104GG>AT (p.Gly35Met) H3.3 histone A was tumor without 12q aberration. In-frame HMGA2-NCOR2 transcripts all In two cases, presence an confirmed by FISH on metaphase spreads.Our results demonstrate that subset are characterized gene.

Language: Английский

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