Article
Neurosciences
Shilpy Jha, Prit Benny Mulgulwar, Mehar Chand Sharma, Suvendu Purkait, Ashis Pattnaik, Mukund Namdev Sable
Summary: Lipogenic differentiation in ependymoma is rare, and there are few reported cases. The grading of this type of ependymoma is based solely on histomorphology and does not include molecular subtyping. This is the first documentation of a fusion negative supratentorial anaplastic ependymoma with lipogenic differentiation.
Article
Oncology
Ashley Patton, Julia A. Bridge, David Liebner, Catherine Chung, O. Hans Iwenofu
Summary: Cutaneous fibromyxoid neoplasms (CFMN) encompass a wide range of benign and malignant tumors with varying treatment implications. This report describes a rare CFMN case featuring a YAP1::TFE3 fusion, morphologically distinct from previously described cases, suggesting a potential new entity within the CFMN spectrum.
GENES CHROMOSOMES & CANCER
(2022)
Article
Pathology
Josephine K. Dermawan, Elizabeth M. Azzato, Steven D. Billings, Karen J. Fritchie, Sebastien Aubert, Armita Bahrami, Marta Barisella, Daniel Baumhoer, Veronika Blum, Beata Bode, Scott W. Aesif, Judith V. M. G. Bovee, Brendan C. Dickson, Mari van den Hout, David R. Lucas, Holger Moch, Gabriel Oaxaca, Alberto Righi, Raf Sciot, Vaiyapuri Sumathi, Akihiko Yoshida, Brian P. Rubin
Summary: YAP1-TFE3-fused hemangioendothelioma is a rare malignant vascular tumor with a female predominance. It commonly occurs in soft tissue and bone. Different histopathological patterns and variable expression of certain proteins, but consistent presence of YAP1-TFE3 gene fusion, were observed. Surgical resection is a common treatment approach and patients generally have a favorable prognosis.
Article
Cell Biology
Frank Szulzewsky, Sonali Arora, Aleena K. S. Arakaki, Philipp Sievers, Damian A. Almiron Bonnin, Patrick J. Paddison, Felix Sahm, Patrick J. Cimino, Taranjit S. Gujral, Eric C. Holland
Summary: The study investigates the role of YAP1-MAML2 gene fusion in the formation of meningioma and demonstrates that YAP1-MAML2 is a causal oncogenic driver in meningioma.
GENES & DEVELOPMENT
(2022)
Article
Developmental Biology
Frank Szulzewsky, Eric C. Holland, Valeri Vasioukhin
Summary: YAP1 is a crucial transcriptional co-activator involved in both normal tissue homeostasis and cancer development. Its activity is regulated by various mechanisms such as the Hippo signaling pathway and miRNAs, and different therapeutic strategies targeting YAP1 functions are being explored.
DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Ziad Bakouny, Ananthan Sadagopan, Praful Ravi, Nebiyou Y. Metaferia, Jiao Li, Shatha AbuHammad, Stephen Tang, Thomas Denize, Emma R. Garner, Xin Gao, David A. Braun, Laure Hirsch, John A. Steinharter, Gabrielle Bouchard, Emily Walton, Destiny West, Chris Labaki, Shaan Dudani, Chun-Loo Gan, Vidyalakshmi Sethunath, Filipe L. F. Carvalho, Alma Imamovic, Cora Ricker, Natalie Vokes, Jackson Nyman, Jacob E. Berchuck, Jihye Park, Michelle S. Hirsch, Rizwan Haq, Gwo-Shu Mary Lee, Bradley A. McGregor, Steven L. Chang, Adam S. Feldman, Catherine J. Wu, David F. McDermott, Daniel Y. C. Heng, Sabina Signoretti, Eliezer M. Van Allen, Toni K. Choueiri, Srinivas R. Viswanathan
Summary: This study comprehensively defines the clinical and molecular features of translocation renal cell carcinoma (tRCC), a subtype of kidney cancer driven by MiT/TFE gene fusions. tRCCs mainly harbor MiT/TFE fusions and homozygous deletions at chromosome 9p21.3, and display a heightened NRF2-driven antioxidant response. Patients with tRCC treated with vascular endothelial growth factor receptor inhibitors (VEGFR-TKIs) have worse outcomes compared to those treated with immune checkpoint inhibitors (ICI). The study findings may inspire new therapeutic hypotheses for tRCC.
Article
Biochemistry & Molecular Biology
McKayla Mickle, Gautam Adhikary, Suruchi Shrestha, Wen Xu, Richard L. Eckert
Summary: VGLL4 inhibits the aggressive cancer phenotype of epidermal SCC by suppressing YAP1/TEAD-dependent pro-cancer signaling, leading to reduced expression of YAP1 target genes and pro-cancer collagen genes.
MOLECULAR CARCINOGENESIS
(2021)
Article
Biochemistry & Molecular Biology
Ru Fang, Xiaotong Wang, Qiuyuan Xia, Ming Zhao, Hao Zhang, Xuan Wang, Shengbing Ye, Kai Cheng, Yan Liang, Yang Cheng, Yayun Gu, Qiu Rao
Summary: The ASPL-TFE3 fusion gene is a common fusion gene in Xp11 translocation renal cell carcinoma (tRCC) and plays a key role in promoting RCC cell proliferation by activating the lysosome-autophagy pathway. This fusion gene escapes regulation by the classic mTOR-TFE3 signal and instead activates phospho-mTOR and its downstream targets. Targeting both autophagy and the mTOR axis may represent a novel treatment strategy for ASPL-TFE3 fusion RCC.
Article
Clinical Neurology
Jian Wang, Liang Wang, Lin Fu, Qing-Chang Li, Xue-Shan Qiu, En-Hua Wang, Juan-Han Yu
Summary: A 26-year-old Chinese man experienced three grand mal seizures in the past two months, and was diagnosed with grade 2 ependymoma with the rare YAP1:FAM118B fusion after surgery.
Article
Pathology
Kathleen M. Schieffer, Vibhuti Agarwal, Stephanie LaHaye, Katherine E. Miller, Daniel C. Koboldt, Tara Lichtenberg, Kristen Leraas, Patrick Brennan, Benjamin J. Kelly, Erin Crist, Jerome Rusin, Jonathan L. Finlay, Diana S. Osorio, Eric A. Sribnick, Jeffrey R. Leonard, Alexander Feldman, Brent A. Orr, Jonathan Serrano, Varshini Vasudevaraja, Matija Snuderl, Peter White, Vincent Magrini, Richard K. Wilson, Elaine R. Mardis, Daniel R. Boue, Catherine E. Cottrell
Summary: Meningiomas, a type of central nervous system tumor, can be associated with the NF2 gene mutation. However, YAP1 fusion meningiomas have been found to exhibit distinct genetic and biological characteristics compared to NF2-driven meningiomas. Both types of meningiomas show overexpression of EGFR and MET, but YAP1 fusion meningiomas have unique histopathological features and a different DNA methylation profile.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2021)
Review
Pathology
Cheng Zou, Guo-qing Ru, Ming Zhao
Summary: Ossifying fibromyxoid tumor (OFMT) is a rare mesenchymal neoplasm that can be subdivided into typical, atypical, and malignant tumors. This case report describes a unique PHF1-TFE3 fusion atypical OFMT with prominent collagenous rosettes, and the patient remained disease-free at 63 months' follow-up.
EXPERIMENTAL AND MOLECULAR PATHOLOGY
(2021)
Article
Pathology
Jeffrey M. Cloutier, Davis R. Ingram, Khalida Wani, Alexander J. Lazar, Wei -Lien Wang
Summary: Synovial sarcoma often shows strong and diffuse expression of TRPS1, a marker associated with breast carcinoma. The expression of TRPS1 in synovial sarcoma is influenced by the SS18-SSX fusion oncoprotein. Understanding TRPS1 expression in synovial sarcoma is crucial for accurate immunohistochemical diagnosis.
Article
Oncology
Jinxiu Li, Timothy S. Mulvihill, Li Li, Jared J. Barrott, Mary L. Nelson, Lena Wagner, Ian C. Lock, Amir Pozner, Sydney Lynn Lambert, Benjamin B. Ozenberger, Michael B. Ward, Allie H. Grossmann, Ting Liu, Ana Banito, Bradley R. Cairns, Kevin B. Jones
Summary: Reduced protein levels of SMARCB1 are seen in synovial sarcoma, but it still plays a defining role within specific BAF complexes. This reduction is driven by SS18-SSX-induced degradation of canonical BAF, leading to shifts in the abundance of other BAF-family subtypes over time.
Article
Neurosciences
Tatsuya Ozawa, Syuzo Kaneko, Frank Szulzewsky, Zhiwei Qiao, Mutsumi Takadera, Yoshitaka Narita, Tadashi Kondo, Eric C. Holland, Ryuji Hamamoto, Koichi Ichimura
Summary: The study revealed that C11orf95-RELA fusion genes are the hallmark of supratentorial ependymomas, with a close association with aberrant NF-kappa B activity. Through ChIP-seq analysis, RNA-Seq data, and transcription factor motif analysis, the study identified the oncogenic pathways orchestrated by both C11orf95 and RELA target genes in ependymoma formation. Further anti-cancer drug screening with mouse ependymoma cells identified potential anti-ependymoma drugs related to the oncogenic mechanism of RELA(FUS).
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Review
Pediatrics
Xuan Zheng, Shaolei Guo, Dawei Liu, Jianping Chu, Yongfu Li, Xiaoxuan Wang, Xing Zhang, Chao Song, Quan Huang
Summary: This study reported a case of pediatric meningioma with a novel MAML2-YAP1 fusion variant. The study also reviewed the relevant literature and suggested that this type of meningioma is more likely to have pathological features of rhabdoid cells. Large-scale studies are needed to validate this finding and explore better integrated diagnosis and treatment methods.
Article
Oncology
Romain Sigaud, Lisa Roesch, Charlotte Gatzweiler, Julia Benzel, Laura von Soosten, Heike Peterziel, Florian Selt, Sara Najafi, Simay Ayhan, Xenia F. Gerloff, Nina Hofmann, Isabel Buedenbender, Lukas Schmitt, Kathrin Foerster, Juergen Burhenne, Walter E. Haefeli, Andrey Korshunov, Felix Sahm, Cornelis M. van Tilburg, David T. W. Jones, Stefan M. Pfister, Deborah Knoerzer, Brent L. Kreider, Max Sauter, Kristian W. Pajtler, Marc Zuckermann, Ina Oehme, Olaf Witt, Till Milde
Summary: The study demonstrates that ulixertinib monotherapy and combination therapies can effectively inhibit pLGG growth, showing promising potential for the treatment of pLGG.
Article
Clinical Neurology
Patrick J. Cimino, Courtney Ketchum, Rust Turakulov, Omkar Singh, Zied Abdullaev, Caterina Giannini, Peter Pytel, Giselle Yvette Lopez, Howard Colman, MacLean P. Nasrallah, Mariarita Santi, Igor Lima Fernandes, Jeff Nirschl, Sonika Dahiya, Stewart Neill, David Solomon, Eilis Perez, David Capper, Haresh Mani, Dario Caccamo, Matthew Ball, Michael Badruddoja, Rati Chkheidze, Sandra Camelo-Piragua, Joseph Fullmer, Sanda Alexandrescu, Gabrielle Yeaney, Charles Eberhart, Maria Martinez-Lage, Jie Chen, Leor Zach, B. K. Kleinschmidt-DeMasters, Marco Hefti, Maria-Beatriz Lopes, Nicholas Nuechterlein, Craig Horbinski, Fausto J. Rodriguez, Martha Quezado, Drew Pratt, Kenneth Aldape
Summary: This study provides further evaluation and classification of high-grade astrocytoma with piloid features (HGAP). The study identifies three distinct subtypes of HGAP and discovers characteristic genetic mutations and epigenetic changes. This research is important for understanding the pathogenesis and clinical characteristics of HGAP.
ACTA NEUROPATHOLOGICA
(2023)
Article
Oncology
Yang Liu, Fu-Ju Chou, Fengchao Lang, Meili Zhang, Hua Song, Wei Zhang, Dionne L. Davis, Nicole J. Briceno, Yang Zhang, Patrick J. Cimino, Kareem A. Zaghloul, Mark R. Gilbert, Terri S. Armstrong, Chunzhang Yang
Summary: This study reveals that mutations of the IDH gene are common in human malignancies and play critical roles in malignant transformation. The PI3K/AKT signaling pathway is enhanced in IDH-mutated cancer cells. Combining the AKT inhibitor Ipa with the genotoxic agent TMZ shows synergistic therapeutic effect in IDH-mutated cancer cells.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Jonas Ecker, Florian Selt, Dominik Sturm, Martin Sill, Andrey Korshunov, Steffen Hirsch, David Capper, Nicola Dikow, Christian Sutter, Carina Mueller, Romain Sigaud, Angelika Eggert, Thorsten Simon, Tim Niehues, Andreas von Deimling, Kristian W. Pajtler, Cornelis M. van Tilburg, David T. W. Jones, Felix Sahm, Stefan M. Pfister, Olaf Witt, Till Milde
Summary: The PTT 2.0 program aims to improve diagnostic accuracy and detect actionable alterations in relapsed pediatric oncology patients, even with limited tumor material. The study utilized molecular analyses such as DNA methylation array, targeted gene panel sequencing, RNA sequencing, and immunohistochemistry to provide relevant and robust information for diagnosis and treatment decisions.
EUROPEAN JOURNAL OF CANCER
(2023)
Review
Oncology
Monika Sparber-Sauer, Andrea Ferrari, Sheri L. Spunt, Christian Vokuhl, Dana Casey, Timothy B. Lautz, William H. Meyer, David O. Walterhouse, Kristian W. Pajtler, Rita Alaggio, Andreas Schmidt, Akmal Safwat, Beate Timmermann, Patrizia Dall'Igna, Sonja Chen, Aaron R. Weiss, Daniel Orbach
Summary: The background discusses the controversial issue of margin status following surgery in pediatric soft tissue sarcomas and the need for international harmonized recommendations. The INSTRuCT NRSTS working group aims to develop common guidelines by pooling and mining clinical trial data from various cooperative groups. This review addresses accepted principles, controversies, and perspectives from different specialties to build a framework for future research.
Article
Clinical Neurology
Henri Bogumil, Martin Sill, Daniel Schrimpf, Britta Ismer, Christina Blume, Ramin Rahmanzade, Felix Hinz, Asan Cherkezov, Rouzbeh Banan, Dennis Friedel, David E. Reuss, Florian Selt, Jonas Ecker, Till Milde, Kristian W. Pajtler, Jens Schittenhelm, Jürgen Hench, Stephan Frank, Henning B. Boldt, Bjarne Winther Kristensen, David Scheie, Linea C. Melchior, Viola Olesen, Astrid Sehested, Daniel R. Boue, Zied Abdullaev, Laveniya Satgunaseelan, Ina Kurth, Annekatrin Seidlitz, Christine L. White, Ho-Keung Ng, Zhi-Feng Shi, Christine Haberler, Martina Deckert, Marco Timmer, Roland Goldbrunner, Arnault Tauziede-Espariat, Pascale Varlet, Sebastian Brandner, Sanda Alexandrescu, Matija Snuderl, Kenneth Aldape, Andrey Korshunov, Olaf Witt, Christel Herold-Mende, Andreas Unterberg, Wolfgang Wick, Stefan M. Pfister, Andreas von Deimling, David T. W. Jones, Felix Sahm, Philipp Sievers
Summary: This study identified a new type of glioneuronal tumor with ATRX alteration, kinase fusion, and anaplastic features. The molecular characteristics of these tumors suggest potential targeted therapies, such as NTRK inhibition.
ACTA NEUROPATHOLOGICA
(2023)
Article
Oncology
Philipp Sievers, Martin Sill, Daniel Schrimpf, Zied Abdullaev, Andrew M. M. Donson, Jessica A. A. Lake, Dennis Friedel, David Scheie, Olli Tynninen, Tuomas Rauramaa, Kaisa L. L. Vepsaelaeinen, David Samuel, Rebecca Chapman, Richard G. G. Grundy, Kristian W. W. Pajtler, Arnault Tauziede-Espariat, Alice Metais, Pascale Varlet, Matija Snuderl, Thomas S. S. Jacques, Kenneth Aldape, David E. E. Reuss, Andrey Korshunov, Wolfgang Wick, Stefan M. M. Pfister, Andreas von Deimling, Felix Sahm, David T. W. Jones
Summary: In this study, a rare type of pediatric high-grade neuroepithelial tumor was investigated using multiple molecular genetic testing methods. Recurrent fusions involving the CIC gene were identified in the tumor samples analyzed. These tumors showed a heterogeneous morphological profile and shared a common DNA methylation signature. Further research is needed to understand the functional consequences of the fusion protein and its potential therapeutic implications.
NPJ PRECISION ONCOLOGY
(2023)
Letter
Clinical Neurology
Allison Shelbourn, Nicholas Nuechterlein, Carolina Angelica Parada, Jessica Eaton, Mallory Tucker, Manuel Ferreira Jr, Patrick J. Cimino
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Review
Oncology
Amir Jassim, Eric P. Rahrmann, Ben D. Simons, Richard J. Gilbertson
Summary: Understanding the combination of cell intrinsic and extrinsic factors in initiating transformation is important for cancer prevention, detection, and early treatment. This review outlines current theories on cancer origins and the underlying determinants of cancer risk. While cancer has been a leading cause of death for decades, controversy remains regarding the transformation of tissues, hindering effective prevention and early intervention. By understanding the complex interplay of cell intrinsic and extrinsic factors, effective strategies for preventing, detecting, and stopping cancer before it becomes incurable can be discovered.
NATURE REVIEWS CANCER
(2023)
Letter
Clinical Neurology
Nicholas Nuechterlein, Allison Shelbourn, Patrick J. Cimino
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kieran Foley, David Shorthouse, Eric Rahrmann, Lizhe Zhuang, Ginny Devonshire, Rebecca C. OCCAMS Consortium, Rebecca C. Fitzgerald, Benjamin A. Hall
Summary: Metastasis in oesophageal adenocarcinoma (OAC) is a crucial factor affecting survival. Radiological staging is commonly used to assess metastases, but its accuracy is limited. This study analyzed lymph node metastases and identified new roles of genes SMAD4 and KCNQ3 in metastasis. The findings suggest that both genes could serve as novel biomarkers for metastatic risk and offer potential new targets for drug treatment.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Meeting Abstract
Oncology
Paul Northcott, Kyle Smith, Rahul Kumar, Leena Paul, Laure Bihannic, Tong Lin, Kendra Maass, Kristian Pajtler, Murali Chintagumpala, Jack Su, Eric Bouffet, Michael Fisher, Sridharan Gururangan, Richard Cohn, Tim Hassall, Jordan Hansford, Paul Klimo, Frederick Boop, Clinton Stewart, Julie Harreld, Thomas Merchant, Ruth Tatevossian, Geoffrey Neale, Matthew Lear, Jeffery Klco, Brent Orr, David Ellison, Richard Gilbertson, Arzu Onar-Thomas, Amar Gajjar, Giles Robinson
Meeting Abstract
Oncology
Konstantin Okonechnikov, Aylin Camgoez, Donglim Esther Park, Owen Chapman, Jens-Martin Huebner, Anne Jenseit, Abhijit Chakraborty, Meghana Pagadala, Rosalind Bump, Sahaana Chandran, Katherina Kraft, Rocio Acuna Hidalgo, Derek Reid, Edwin F. Juarez, James T. Robinson, Kristian W. Pajtler, Till Milde, Nicole Coufal, Michael Levy, Denise Malicki, Shareef Nahas, Matija Snuderl, John Crawford, Robert Wechsler-Reya, Stefan Mundlos, Anthony Schmitt, Hannah Carter, Kulandaimanuvel Antony Michealraj, Sachin A. Kumar, Michael D. Taylor, Jeremy Rich, Jill Mesirov, Stefan P. Pfister, Ferhat Ay, Jesse Dixon, Marcel Kool, Lukas Chavez
Meeting Abstract
Oncology
Anna Kolodziejczak, Florian Selt, Heike Peterziel, Nora Jamaladdin, Norman Mack, Kendra Maass, Marcel Kool, Christel Herold-Mende, Ahmed El Damaty, Ina Oehme, David T. W. Jones, Olaf Witt, Kristian W. Pajtler, Christian Kratz, Stefan M. Pfister, Till Milde
Meeting Abstract
Oncology
Holly Lindsay, Maura Massimino, Shivaram Avula, Stavros Stivaros, Richard Grundy, Katie Metrock, Aashim Bhatia, Ana Fernandez-Teijeiro, Luisa Chiapparini, Jeffrey Bennett, Karen Wright, Lindsey Hoffman, Amy Smith, Kristian Pajtler, Tina Young Poussaint, Katherine Warren, Nicholas Foreman, David Mirsky