Review
Clinical Neurology
Anne Jenseit, Aylin Camgoz, Stefan M. Pfister, Marcel Kool
Summary: Ependymomas are tumors of the central nervous system that can occur in different anatomical compartments, with distinct molecular subtypes identified through profiling studies. PFA ependymomas, the most common group, are characterized by a young age at diagnosis, balanced genome, and poor clinical outcomes. Research suggests the disease is primarily driven by epigenetics.
ACTA NEUROPATHOLOGICA
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Thomas Leclerc, Raphael Levy, Arnault Tauziede-Espariat, Charles-Joris Roux, Kevin Beccaria, Thomas Blauwblomme, Stephanie Puget, Jacques Grill, Christelle Dufour, Lea Guerrini-Rousseau, Samuel Abbou, Stephanie Bolle, Alexandre Roux, Johan Pallud, Corentin Provost, Catherine Oppenheim, Pascale Varlet, Nathalie Boddaert, Volodia Dangouloff-Ros
Summary: The MRI characteristics of posterior fossa ependymoma subtypes, EPN_PFA and EPN_PFB, can be distinguished. EPN_PFA is commonly seen in young children and appears as median or lateral tissular calcified masses with incomplete enhancement, pronounced hydrocephalus, and invasion of the posterior fossa foramina. EPN_PFB is commonly seen in adolescents and adults as median non-calcified masses, predominantly cystic, minimally invasive, with total and homogeneous enhancement.
EUROPEAN RADIOLOGY
(2023)
Review
Pediatrics
Cleiton Formentin, Andrei Fernandes Joaquim, Enrico Ghizoni
Summary: Pediatric posterior fossa tumors have a higher incidence rate compared to adult tumors. Molecular biomarkers play a crucial role in the diagnosis, prognosis, and treatment of these tumors. The current treatment strategy is mainly based on surgical resection, but molecular targeted therapies are also being explored.
EUROPEAN JOURNAL OF PEDIATRICS
(2023)
Article
Neurosciences
Cassandra Mariet, David Castel, Jacques Grill, Raphael Saffroy, Volodia Dangouloff-Ros, Nathalie Boddaert, Francisco Llamas-Guttierrez, Celine Chappe, Stephanie Puget, Lauren Hasty, Fabrice Chretien, Alice Metais, Pascale Varlet, Arnault Tauziede-Espariat
Summary: This study retrospectively investigated 9 cases of pediatric H3 K27M-mutant EPN_PFA and found that 7 tumors clustered with EPN_PFA, while one was reclassified as DMG. H3 K27M-mutant EPN_PFA cases were older and showed similarities in radiology and histopathology with EZHIP-overexpressing EPN_PFA. Sequencing analysis revealed K27M mutations in HIST1H3B, HIST1H3C, H3F3A, and HIST1H3D. Overall survival rates were similar between EZHIP-overexpressing and H3 K27M-mutant EPN_PFA.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Guanyi Wang, Yibin Jia, Yuqin Ye, Enming Kang, Huijun Chen, Jiayou Wang, Xiaosheng He
Summary: Through methods like WGCNA analysis, key hub genes for EPN-PF were identified, indicating their involvement in multiple important cellular signaling pathways that may impact patient prognosis.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Andrew M. Donson, Kelsey C. Bertrand, Kent A. Riemondy, Dexiang Gao, Yonghua Zhuang, Bridget Sanford, Gregory A. Norris, Rebecca J. Chapman, Rui Fu, Nicholas Willard, Andrea M. Griesinger, Graziella Ribeiro de Sousa, Vladimir Amani, Enrique Grimaldo, Todd C. Hankinson, Ffyona Booker, Martin Sill, Richard G. Grundy, Kristian W. Pajtler, David W. Ellison, Nicholas K. Foreman, Timothy A. Ritzmann
Summary: The study focuses on the biology of recurrent PFA and reveals that chromosomal changes at recurrence are associated with poor prognosis. The genetic evolution of neoplastic cells leads to cellular heterogeneity in PFAs.
Article
Medicine, General & Internal
Stefania Picariello, Pietro Spennato, Jonathan Roth, Nir Shimony, Alessandra Marini, Lucia De Martino, Giancarlo Nicosia, Giuseppe Mirone, Maria Serena De Santi, Fabio Savoia, Maria Elena Errico, Lucia Quaglietta, Shlomi Costantini, Giuseppe Cinalli
Summary: This study retrospectively reviewed a cohort of infants with posterior fossa tumors (PFTs) treated from 2007 to 2018, reporting on the pathological characteristics, surgical aspects, and treatment outcomes of these tumors. The study found that infants with high-grade tumors had significantly lower progression-free survival and overall survival rates, indicating the need for more effective strategies.
Article
Oncology
Aruna Nambirajan, Agrima Sharma, Madhu Rajeshwari, Meher Tej Boorgula, Ramesh Doddamani, Ajay Garg, Vaishali Suri, Chitra Sarkar, Mehar Sharma
Summary: This study demonstrates that H3K27me3 is a robust surrogate for subgrouping PF-EPNs. EZHIP overexpression and 1q gain are unique features in PFA, with Tenascin C being more frequently positive. Additionally, H3K27M mutations and ATRX loss show distinct patterns in PFA-EPNs.
BRAIN TUMOR PATHOLOGY
(2021)
Article
Clinical Neurology
Ying Jin, Dan Cheng, Yunyun Duan, Zhizheng Zhuo, Jinyuan Weng, Chengzhou Zhang, Mingwang Zhu, Xing Liu, Jiang Du, Tiantian Hua, Hongfang Li, Sven Haller, Frederik Barkhof, Yaou Liu
Summary: The purpose of this study was to investigate the predictive value of the soap bubble sign on molecular subtypes of posterior fossa ependymomas (PF-EPNs). The soap bubble sign was observed in PFB cases but not in PFA cases. The findings suggest that the soap bubble sign is a highly specific imaging marker for the PFB molecular subtype of PF-EPNs.
Article
Genetics & Heredity
Roberto Paparella, Anna Maria Caroleo, Emanuele Agolini, Giovanni Chillemi, Evelina Miele, Lucia Pedace, Martina Rinelli, Simone Pizzi, Luigi Boccuto, Giovanna Stefania Colafati, Mariachiara Lodi, Antonella Cacchione, Andrea Carai, Maria Cristina Digilio, Paolo Toma, Marco Tartaglia, Angela Mastronuzzi
Summary: Variants in the POLR2A gene may be associated with symptoms such as infantile-onset hypotonia and developmental delay. This study describes a case of ependymoma in a 2-year-old male with a de novo pathogenic variant in the POLR2A gene.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Correction
Oncology
Aruna Nambirajan, Agrima Sharma, Madhu Rajeshwari, Meher Tej Boorgula, Ramesh Doddamani, Ajay Garg, Vaishali Suri, Chitra Sarkar, Mehar Chand Sharma
Summary: The middle name of the corresponding author was missing in the original publication of the article.
BRAIN TUMOR PATHOLOGY
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
J. M. Lieb, A. Lonak, A. Vogler, F. Pruefer, F. J. Ahlhelm
Summary: Tumors of the posterior fossa account for a significant portion of brain tumors in childhood, and differential diagnosis relies on tumor location, patient age, and intratumoral diffusion assessed by diffusion-weighted imaging using MRI. Advanced MR techniques like MRI perfusion and MR spectroscopy can provide additional assistance in the initial diagnosis and monitoring of these tumors.
Article
Multidisciplinary Sciences
Jichang Han, Xiaomin Song, Yachao Liu, Lin Li
Summary: The CXorf6 (chromosome X open reading frame 67) protein has been predicted to be mostly disordered and its functions have long been limited due to low expression in most cells and tissues. However, recent studies have discovered its high expression specifically in posterior fossa A (PFA) ependymomas, a malignant and aggressive type of brain tumor. Notably, CXorf67 has been found to inhibit PRC2 enzymatic activity, leading to a reduction in H3K27me3 levels in PFA ependymomas. Additionally, it has been shown to block DNA homologous recombination repair through inhibiting PALB2-BRCA2 interaction. These findings suggest that CXorf67 could serve as a promising therapeutic target and biomarker for PFA ependymomas, as well as potentially for other types of tumors.
CHINESE SCIENCE BULLETIN-CHINESE
(2022)
Article
Clinical Neurology
Beatrice C. Bono, Marco Riva, Federico Pessina
Summary: The study describes a surgical technique combining the telovelar-posterolateral approach for the resection of a giant posterior fossa ependymoma. The postoperative MRI scan showed near complete removal of the tumor and the patient was discharged neurologically intact. This approach allows for a single-stage surgical procedure and near total resection of complex giant tumors.
ACTA NEUROCHIRURGICA
(2023)
Article
Clinical Neurology
Ido Ben Zvi, Gideon Adegboyega, Sebastian M. Toescu, Noa Schwartz, Amir Kershenovich, Helen Toledano, Shalom Michowiz, Kristian Aquilina
Summary: This study revealed that postoperative cerebrospinal fluid (CSF) diversion procedures may cause a preventable delay in the initiation of adjuvant therapy (AT). It is suggested that early post-operative VP shunt insertion, rather than a 'wait and see policy', should be considered in order to reduce this delay. Multivariable linear regression modeling did not show a significant effect of VPS or mCPPRH on progression-free survival or OS.
CHILDS NERVOUS SYSTEM
(2022)
Article
Oncology
Florian Selt, Romain Sigaud, Gintvile Valinciute, Philipp Sievers, Julia Zaman, Clara Alco, Simone Schmid, Heike Peterziel, Jessica W. Tsai, Romain Guiho, Juan Pedro Martinez-Barbera, Stefan Pusch, Jing Deng, Yifan Zhai, Cornelis M. van Tilburg, Martin U. Schuhman, Ahmed E. L. Damaty, Pratiti Bandopadhayay, Christel Herold-Mende, Andreas von Deimling, Stefan M. Pfister, Joan Montero, David Capper, Ina Oehme, Felix Sahm, David T. W. Jones, Olaf Witt, Till Milde
Summary: Our study demonstrates that BCL-XL is critical for the survival of senescent PA tumor cells and provides evidence for the use of clinically available BCL-XL-dependent senolytic agents.
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)
Article
Oncology
Marie Morfouace, Peter Horak, Simon Kreutzfeldt, Aleksandra Stevovic, Teresa de Rojas, Evgeniya Denisova, Barbara Hutter, Francisco Bautista, Anne -Sophie Defachelles, Jeff White, Julio Oliveira, Bernd Kasper, Matthias Preusser, Vassilis Golfinopoulos, Stefan Pfister, Winette Van der Graaf, Eva Wardelmann, Patrick Shenjere, Stefan Froehling, Martin G. McCabe
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
Cell Biology
Mariam G. Aslanyan, Cenna Doornbos, Gaurav D. Diwan, Zeinab Anvarian, Tina Beyer, Katrin Junger, Sylvia E. C. van Beersum, Robert B. Russell, Marius Ueffing, Alexander Ludwig, Karsten Boldt, Lotte B. Pedersen, Ronald Roepman
Summary: By studying ubiquitination modifications in cells, we have identified the involvement of ESCRT-dependent clathrin-mediated endocytosis vesicles and caveolae components in ciliary function. These findings contribute to a better understanding of the mechanisms underlying cilia biology in health and disease.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Oncology
Venu Thatikonda, S. M. Ashiqul Islam, Robert J. Autry, Barbara C. Jones, Susanne N. Groebner, Gregor Warsow, Barbara Hutter, Daniel Huebschmann, Stefan Froehling, Marcel Kool, Mirjam Blattner-Johnson, David T. W. Jones, Ludmil B. Alexandrov, Stefan M. Pfister, Natalie Jaeger
Summary: Jager and colleagues analyzed the mutational patterns in pediatric cancers and found marked differences compared to adult cancers, providing insights into molecular mechanisms. They identified a small number of mutational signatures specific to pediatric cancers and discovered a previously unreported indel signature in pediatric leukemias. This study provides a systematic overview of mutational signatures in pediatric cancers, which is highly relevant for understanding tumor biology and developing biomarkers for treatment response.
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)
Letter
Oncology
Christian P. Kratz, Dmitrii Smirnov, Robert Autry, Natalie Jaeger, Sebastian M. Waszak, Anika Grosshennig, Riccardo Berutti, Mareike Wendorff, Pierre Hainaut, Stefan M. Pfister, Holger Prokisch, Tim Ripperger, David Malkin
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Biochemistry & Molecular Biology
Dominik Sturm, David Capper, Felipe Andreiuolo, Marco Gessi, Christian Koelsche, Annekathrin Reinhardt, Philipp Sievers, Annika K. Wefers, Azadeh Ebrahimi, Abigail K. Suwala, Gerrit H. Gielen, Martin Sill, Daniel Schrimpf, Damian Stichel, Volker Hovestadt, Bjarne Daenekas, Agata Rode, Stefan Hamelmann, Christopher Previti, Natalie Jaeger, Ivo Buchhalter, Mirjam Blattner-Johnson, Barbara C. Jones, Monika Warmuth-Metz, Brigitte Bison, Kerstin Grund, Christian Sutter, Steffen Hirsch, Nicola Dikow, Martin Hasselblatt, Ulrich Schueller, Nicolas U. Gerber, Christine L. White, Molly K. Buntine, Kathryn Kinross, Elizabeth M. Algar, Jordan R. Hansford, Nicholas G. Gottardo, Pablo Hernaiz Driever, Astrid Gnekow, Olaf Witt, Hermann L. Mueller, Gabriele Calaminus, Gudrun Fleischhack, Uwe Kordes, Martin Mynarek, Stefan Rutkowski, Michael C. Fruehwald, Christof M. Kramm, Andreas von Deimling, Torsten Pietsch, Felix Sahm, Stefan M. Pfister, David. T. W. Jones
Summary: This study prospectively integrated DNA methylation profiling and targeted gene panel sequencing to evaluate their utility in routine neuropathology for newly diagnosed pediatric patients with CNS tumors. The integration of multi-omics improved diagnostic accuracy by refining DNA methylation classification, detecting relevant genetic alterations, and identifying cancer predisposition syndromes. Discrepancies between neuropathological classification and DNA methylation classification were particularly relevant for high-grade gliomas, and patients with lower-grade molecular profiles had improved survival.
Article
Oncology
Emily C. Hardin, Simone Schmid, Alexander Sommerkamp, Carina Bodden, Anna-Elisa Heipertz, Philipp Sievers, Andrea Wittmann, Till Milde, Stefan M. Pfister, Andreas von Deimling, Svea Horn, Nina A. Herz, Michele Simon, Ashwyn A. Perera, Amedeo Azizi, Ofelia Cruz, Sarah Curry, An Van Damme, Miklos Garami, Darren Hargrave, Antonis Kattamis, Barbara Faganel Kotnik, Paeivi Laehteenmaeki, Katrin Scheinemann, Antoinette Y. N. Schouten-van Meeteren, Astrid Sehested, Elisabetta Viscardi, Ole Mikal Wormdal, Michal Zapotocky, David S. Ziegler, Arend Koch, Pablo Hernaiz Driever, Olaf Witt, David Capper, Felix Sahm, David T. W. Jones, Cornelis M. van Tilburg
Summary: The addition of RNA-Seq to current diagnostic methods improves diagnostic accuracy, making precision oncology treatments more accessible for pediatric low-grade glioma (pLGG) patients. The study suggests including RNA-Seq as part of routine diagnostics, especially when no common pLGG alteration is identified.
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)
Review
Biochemistry & Molecular Biology
Fabiola De Marchi, Toni Franjkic, Paride Schito, Tommaso Russo, Jerneja Nimac, Anna A. Chami, Angelica Mele, Lea Vidatic, Jasna Kriz, Jean-Pierre Julien, Gordana Apic, Robert B. Russell, Boris Rogelj, Jason R. Cannon, Marco Baralle, Federica Agosta, Silva Hecimovic, Letizia Mazzini, Emanuele Buratti, Ivana Munitic
Summary: Proteinopathy and neuroinflammation are two main features of neurodegenerative diseases with high heterogeneity. This review focuses on ALS and FTD spectrum disorder, highlighting neuroinflammation and immune imbalance as novel therapeutic targets. Dysregulation of TDP-43 is a common mechanism in most ALS and 50% of FTD patients, leading to altered cellular events. Experimental attempts targeting TDP-43 aggregates and inflammation will be discussed.
Article
Oncology
Konstantin Okonechnikov, Piyush Joshi, Mari Sepp, Kevin Leiss, Ioannis Sarropoulos, Florent Murat, Martin Sill, Pengbo Beck, Kenneth Chun-Ho Chan, Andrey Korshunov, Felix Sah, Maximilian Y. Deng, Dominik Sturm, John DeSisto, Andrew M. Donson, Nicholas K. Foreman, Adam L. Green, Giles Robinson, Brent A. Orr, Qingsong Gao, Emily Darrow, Jennifer L. Hadley, Paul A. Northcott, Johannes Gojo, Daisuke Kawauchi, Volker Hovestadt, Mariella G. Filbin, Andreas von Deimling, Marc Zuckermann, Kristian W. Pajtler, Marcel Kool, David T. W. Jones, Natalie Jaeger, Lena M. Kutscher, Henrik Kaessmann, Stefan M. Pfister
Summary: This study successfully identified the cellular origins of the three most common pediatric brain tumors and identified potential therapeutic targets based on the tumor-specific genes expressed in these cellular origins.
Article
Cell Biology
Grace Mercedes Freke, Tiago Martins, Rosalind Jane Davies, Tina Beyer, Marian Seda, Emma Peskett, Naila Haq, Avishek Prasai, Georg Otto, Jeshmi Jeyabalan Srikaran, Victor Hernandez, Gaurav D. Diwan, Robert B. Russell, Marius Ueffing, Martina Huranova, Karsten Boldt, Philip L. Beales, Dagan Jenkins
Summary: Bardet-Biedl syndrome is a ciliopathy that affects multiple tissues. Research suggests that BBS1 plays a crucial role in suppressing the transition from epithelial cells to mesenchymal cells, and dysregulation of epithelial-to-mesenchymal transition genes may be a predisposing feature of BBS.