Article
Clinical Neurology
Pascal D. Johann, Lea Altendorf, Emma-Maria Efremova, Till Holsten, Mona Steinbuegl, Karolina Nemes, Alicia Eckhardt, Catena Kresbach, Michael Bockmayr, Arend Koch, Christine Haberler, Manila Antonelli, John DeSisto, Martin U. Schuhmann, Peter Hauser, Reiner Siebert, Susanne Bens, Marcel Kool, Adam L. Green, Martin Hasselblatt, Michael C. Fruehwald, Ulrich Schueller
Summary: This study investigated the molecular characteristics of recurrent AT/RT tumors compared to their matched primary tumors. It found that there were subtle molecular changes, with chromosome 1q gain and chromosome 10 loss being the most common alterations in recurrences. These findings may help identify novel therapeutic targets for AT/RT recurrences.
ACTA NEUROPATHOLOGICA
(2023)
Article
Gastroenterology & Hepatology
Yael Haberman, Najeeha T. Iqbal, Sudhir Ghandikota, Indika Mallawaarachchi, Tzipi Braun, Phillip J. Dexheimer, Najeeb Rahman, Rotem Hadar, Kamran Sadiq, Zubair Ahmad, Romana Idress, Junaid Iqbal, Sheraz Ahmed, Aneeta Hotwani, Fayyaz Umrani, Lubaina Ehsan, Greg Medlock, Sana Syed, Chris Moskaluk, Jennie Z. Ma, Anil G. Jegga, Sean R. Moore, Syed Asad Ali, Lee A. Denson
Summary: The study found that Environmental Enteric Dysfunction (EED) leads to the suppression of antioxidant, detoxification, and lipid metabolism genes, while inducing the expression of antimicrobial response, interferon, and lymphocyte activation genes. EED also shows hypermethylation of epithelial metabolism and barrier function genes, and hypomethylation of immune response and cell proliferation genes. In addition, EED is associated with lymphocyte proliferation, expression of epithelial metabolism genes, and severity of histological damage, fecal energy loss, and malnutrition.
Article
Multidisciplinary Sciences
Jennifer Cantley, Xiaofen Ye, Emma Rousseau, Tom Januario, Brian D. Hamman, Christopher M. Rose, Tommy K. Cheung, Trent Hinkle, Leofal Soto, Connor Quinn, Alicia Harbin, Elizabeth Bortolon, Xin Chen, Roy Haskell, Eva Lin, Shang-Fan Yu, Geoff Del Rosario, Emily Chan, Debra Dunlap, Hartmut Koeppen, Scott Martin, Mark Merchant, Matt Grimmer, Fabio Broccatelli, Jing Wang, Jennifer Pizzano, Peter S. Dragovich, Michael Berlin, Robert L. Yauch
Summary: This study reports the discovery of a potent and selective SMARCA2 proteolysis-targeting chimera molecule (PROTAC), A947. The authors demonstrate that selective SMARCA2 degradation can be achieved in the absence of selective SMARCA2/4 PROTAC binding, resulting in potent in vitro growth inhibition and in vivo efficacy in SMARCA4 mutant models. The study highlights a potential new therapeutic opportunity for patients with SMARCA4 mutations.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Mamy Andrianteranagna, Joanna Cyrta, Julien Masliah-Planchon, Karolina Nemes, Alice Corsia, Amaury Leruste, Doerthe Holdhof, Uwe Kordes, Daniel Orbach, Nadege Corradini, Natacha Entz-Werle, Gaelle Pierron, Marie-Pierre Castex, Anne Brouchet, Noelle Weingertner, Dominique Ranchere, Paul Freneaux, Olivier Delattre, Jonathan Bush, Alexandra Leary, Michael C. Fruehwald, Ulrich Schueller, Nicolas Servant, Franck Bourdeaut
Summary: ECRTSMARCA4 and ECRTSMARCB1 share similar clinical, pathological, and genomic features, with ECRTSMARCA4 showing closer relationship to SCCOHT. Lack of SMARCA4 and SMARCA2 expression at the protein level is observed in ECRTSMARCA4.
JOURNAL OF PATHOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Sophie M. Navickas, Katherine A. Giles, Kate H. Brettingham-Moore, Phillippa C. Taberlay
Summary: The chromatin remodeler SMARCA4/BRG1 plays a key role in brain tumour development, with its function varying in different tumour types and subtypes. Altered SMARCA4 expression is associated with various brain tumours, and mutations primarily occur in the catalytic ATPase domain, which has tumour suppressor activity. However, SMARCA4 can also promote tumourigenesis through overexpression. This review explores the complex interaction between SMARCA4 and different brain cancer types, highlighting its role in tumour pathogenesis, regulated pathways, and advances in understanding the functional relevance of mutations. The potential of targeting SMARCA4 as adjuvant therapy to enhance current brain cancer treatment methods is also discussed.
Article
Pathology
Srishti Gupta, Sean W. Noona, Stefan E. Pambuccian, Brian Robinson, Linda W. Martin, Eli Williams, Edward B. Stelow, Shyam S. Raghavan
Summary: Undifferentiated SMARCA4-deficient carcinoma of the esophagus and gastroesophageal junction is a rare and highly aggressive malignancy. This case series presents high-grade undifferentiated malignant neoplasms with SMARCA4 loss and a rhabdoid phenotype. The study identifies common immunoreactivity and genetic abnormalities in these cases.
Review
Biochemistry & Molecular Biology
Aaron Shaykevich, Isaac Silverman, Gargi Bandyopadhyaya, Radhashree Maitra
Summary: BRG1 acts as both a tumor suppressor and an oncogene in cancer. Targeted knockout of BRG1 can effectively suppress tumor growth in most cancers. BRG1 plays a role in autophagy, apoptosis, and the Ras/Raf/MAPK/ERK1/2 pathway, affecting cancer proliferation. It interacts with PRMT5 and other proteins to regulate gene expression. Understanding the interaction of BRG1 with cellular pathways can aid in the development of cancer treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Uwe Schwartz, Maria Llamazares Prada, Stephanie T. Pohl, Mandy Richter, Raluca Tamas, Michael Schuler, Corinna Keller, Vedrana Mijosek, Thomas Muley, Marc A. Schneider, Karsten Quast, Joschka Hey, Claus P. Heussel, Arne Warth, Hauke Winter, Oezdemirhan Sercin, Harry Karmouty-Quintana, Soma S. K. Jyothula, Manish K. Patel, Felix Herth, Ina Koch, Giuseppe Petrosino, Alexandru Titimeaua, Balca R. Mardin, Dieter Weichenhan, Tomasz P. Jurkowski, Charles D. Imbusch, Benedikt Brors, Vladimir Benes, Birgit Jung, David Wyatt, Heiko F. Stahl, Christoph Plass, Renata Z. Jurkowska
Summary: Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. We hypothesized that COPD is associated with altered epigenetic signaling in lung cells. We generated genome-wide DNA methylation maps of primary human lung fibroblasts (HLFs) across COPD stages and found early epigenetic changes in COPD, predominantly in regulatory regions. Dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization were observed. Furthermore, we identified candidate regulators and demonstrated the potential for novel therapeutic avenues for COPD patients.
Article
Plant Sciences
Zeyu Zhang, Huihui Wang, Yongsheng Wang, Feihu Xi, Huiyuan Wang, Markus Kohnen, Pengfei Gao, Wentao Wei, Kai Chen, Xuqing Liu, Yubang Gao, Ximei Han, Kaiqiang Hu, Hangxiao Zhang, Qiang Zhu, Yushan Zheng, Bo Liu, Ayaz Ahmad, Yau-Heiu Hsu, Steven E. Jacobsen, Lianfeng Gu
Summary: The study found that CHH methylation gradually accumulates during the transition from vegetative to reproductive growth in moso bamboo, with differentially methylated regions mainly occurring at transcription start and termination sites. Genes with CG methylation changes are enriched in 'vegetative to reproductive phase transition of meristem' GO categories, while circRNA flanking introns are hypermethylated and enriched in LTR retrotransposons.
Review
Genetics & Heredity
Junjie Zhang, Shuilian Xie, Jingxiang Xu, Hui Liu, Shaogui Wan
Summary: Nanopore sequencing technology allows for direct detection of base modifications in DNA and RNA, compared to bisulfite sequencing. The CRISPR/Cas9-targeted enrichment nanopore sequencing techniques are simple and cost-effective, particularly when targeting specific genomic regions.
FRONTIERS IN GENETICS
(2021)
Article
Oncology
Ping Zhou, Yiyun Fu, Weiya Wang
Summary: This study reported two rare cases of GI NEC with SMARCA4 deficiency and described their clinicopathological, radiographic, and histopathological features. SMARCA4 may be a promising targetable and prognostic biomarker.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Xiangpeng Meng, Jia Ma, Nan Meng, Tianyu Yun, Beifang Niu
Summary: SMARCA4 (BRG1)-deficient undifferentiated carcinoma is a rare and aggressive malignancy that can occur in various organs. This is the first reported case of SMARCA4 (BRG1)-deficient undifferentiated carcinoma of the gallbladder, with comprehensive genetic analysis suggesting additional genetic changes involved in tumorigenesis. Somatic mutations in CTNNB1, KRAS, PIK3CA, TP53, CREBBP, and FANCI genes were identified.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Michael Bockmayr, Kim Harnisch, Lara C. Pohl, Leonille Schweizer, Theresa Mohme, Meik Korner, Malik Alawi, Abigail K. Suwala, Mario M. Dorostkar, Camelia M. Monoranu, Martin Hasselblatt, Annika K. Wefers, David Capper, Juergen Hench, Stephan Frank, Timothy E. Richardson, Ivy Tran, Elisa Liu, Matija Snuderl, Lara Engertsberger, Martin Benesch, Andreas von Deimling, Denise Obrecht, Martin Mynarek, Stefan Rutkowski, Markus Glatzel, Julia E. Neumann, Ulrich Schueller
Summary: This study identified two molecular subtypes, MPE-A and MPE-B, of myxopapillary ependymoma (MPE) based on DNA methylation profiling, and found significant differences in progression-free survival between the two subtypes. MPE-A subtype is characterized by younger age, specific tumor morphology, and high methylation level, with a higher relapse rate. MPE-B subtype, on the other hand, has older age, better prognosis, and lower relapse rate.
Article
Biochemistry & Molecular Biology
Alessia Russo, Clara Viberti, Katia Mareschi, Elisabetta Casalone, Simonetta Guarrera, Giovanni Birolo, Giovanni Cazzaniga, Lilia Corral, Luca Trentin, Giuseppe Basso, Franca Fagioli, Giuseppe Matullo
Summary: The KMT2A/AFF1 rearrangement is associated with a poor prognosis in infant acute lymphocytic leukemia (ALL); discordant ALL in monozygotic twins is rare and can be used to evaluate the intrauterine environment-genetic interplay in ALL; genetic analyses at birth provided insights into the timing of mutation hit and identified correlations between DNA methylation and gene expression changes in ALL infants with KMT2A/AFF1 fusions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Plant Sciences
Tania Chakraborty, Hayden Payne, Rebecca A. Mosher
Summary: The revolution in sequencing has provided a wealth of plant genomes for studying the evolution of biological complexity. Gene duplication drives complexity, and angiosperms encode various gene silencing pathways. Recent phylogenetic analysis reveals the expansion, specialization, and occasional contraction of these pathways.
CURRENT OPINION IN PLANT BIOLOGY
(2022)
Editorial Material
Materials Science, Ceramics
A. H. Heuer, M. W. Finnis, W. M. C. Foulkes, A. P. Chen
Summary: This paper comments on recent observations of O and Al self-diffusion in single-crystal sapphire with variable doping concentrations of Mg and Ti. The study suggests that the null effect of aliovalent doping on oxygen diffusivity may be attributed to dopant evaporation near the surface due to extensive heat treatment, whereas an effect on Al diffusivity is still discernible. Furthermore, buffering mechanisms are proposed to be ultimately responsible for modest increases of self-diffusion with respect to dopant concentrations.
JOURNAL OF THE EUROPEAN CERAMIC SOCIETY
(2022)
Article
Oncology
Santhosh A. Upadhyaya, Olivia Campagne, Catherine A. Billups, Brent A. Orr, Arzu Onar-Thomas, Ruth G. Tatevossian, Roya Mostafavi, Jason R. Myers, Anna Vinitsky, Daniel C. Moreira, Holly B. Lindsay, Lindsay Kilburn, Patricia Baxter, Amy Smith, John R. Crawford, Sonia Partap, Anne E. Bendel, Dolly G. Aguilera, Kim E. Nichols, Evadnie Rampersaud, David W. Ellison, Paul Klimo, Zoltan Patay, Giles W. Robinson, Alberto Broniscer, Clinton F. Stewart, Cynthia Wetmore, Amar Gajjar
Summary: This study examines the use of Aurora kinase A inhibitor alisertib in children with recurrent AT/RT. The results show that alisertib is well tolerated in children with recurrent AT/RT, and approximately one-third of the patients observed stable disease or partial response.
Article
Oncology
Karolina Nemes, Pascal D. Johann, Mona Steinbuegl, Miriam Gruhle, Susanne Bens, Denis Kachanov, Margarita Teleshova, Peter Hauser, Thorsten Simon, Stephan Tippelt, Wolfgang Eberl, Martin Chada, Vicente Santa-Maria Lopez, Lorenz Grigull, Pablo Hernaiz-Driever, Matthias Eyrich, Jane Pears, Till Milde, Harald Reinhard, Alfred Leipold, Marianne van de Wetering, Maria Joao Gil-da-Costa, Georg Ebetsberger-Dachs, Kornelius Kerl, Andreas Lemmer, Heidrun Boztug, Rhoikos Furtwaengler, Uwe Kordes, Christian Vokuhl, Martin Hasselblatt, Brigitte Bison, Thomas Kroencke, Patrick Melchior, Beate Timmermann, Joachim Gerss, Reiner Siebert, Michael C. Fruehwald
Summary: Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. A retrospective study was conducted to assess the prognostic factors, genetics, toxicity of treatment and long-term outcomes of MRT. The study found that female sex, localized stage, absence of a GLM, and maintenance therapy were significant predictors of a favorable prognosis in infants with MRT.
Article
Clinical Neurology
Martin Mynarek, Denise Obrecht, Martin Sill, Dominik Sturm, Katja Kloth-Stachnau, Florian Selt, Jonas Ecker, Katja von Hoff, Bjoern-Ole Juhnke, Tobias Goschzik, Torsten Pietsch, Michael Bockmayr, Marcel Kool, Andreas von Deimling, Olaf Witt, Ulrich Schuller, Martin Benesch, Nicolas U. Gerber, Felix Sahm, David T. W. Jones, Andrey Korshunov, Stefan M. Pfister, Stefan Rutkowski, Till Milde
Summary: This study investigates the integration of clinical and molecular parameters to improve risk stratification of non-WNT/non-SHH medulloblastoma (MB). The combination of subgroup and whole-chromosomal aberration (WCA) phenotype was found to be the best predictor of disease progression and death. The identification of low-risk and very high-risk strata through the integration of clinical and molecular variables may improve future treatment stratification.
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Federico Roncaroli, Shivaram Avula, Martin G. McCabe, James T. Hayden, Pieter Wesseling, Ingrid Ora, Monica Nister, Mariette E. G. Kranendonk, Bastiaan B. J. Tops, Michal Zapotocky, Josef Zamecnik, Alexandre Vasiljevic, Tanguy Fenouil, David Meyronet, Katja von Hoff, Ulrich Schuller, Hugues Loiseau, Dominique Figarella-Branger, Christof M. Kramm, Dominik Sturm, David Scheie, Tuomas Rauramaa, Jouni Pesola, Johannes Gojo, Christine Haberler, Sebastian Brandner, Tom Jacques, Alexandra Sexton Oates, Richard Saffery, Ewa Koscielniak, Suzanne J. Baker, Stephen Yip, Matija Snuderl, Nasir Ud Din, David Samuel, Kathrin Schramm, Mirjam Blattner-Johnson, Florian Selt, Jonas Ecker, Till Milde, Andreas von Deimling, Andrey Korshunov, Arie Perry, Stefan M. Pfister, Felix Sahm, David A. Solomon, David T. W. Jones
Summary: Pediatric central nervous system (CNS) tumors are the leading cause of cancer-related death in children aged 0-14 years. A newly identified CNS tumor type characterized by PLAGL1/2 amplification and a lack of recurrent genetic alterations has been described. These tumors are composed of primitive embryonal-like cells and are associated with intermediate survival, but the cell of origin and optimal treatment strategies are yet to be determined.
ACTA NEUROPATHOLOGICA
(2023)
Article
Chemistry, Analytical
Georgina D. Barnabas, Verena Goebeler, Janice Tsui, Jonathan W. Bush, Philipp F. Lange
Summary: This study presents an optimized workflow for efficient protein extraction from FFPE sections, resulting in high proteome coverage and quantitative reproducibility. The ASAP workflow offers a streamlined and cost-effective approach for high-throughput FFPE proteomics.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Philipp Keyl, Philip Bischoff, Gabriel Dernbach, Michael Bockmayr, Rebecca Fritz, David Horst, Nils Bluethgen, Gregoire Montavon, Klaus-Robert Mueller, Frederick Klauschen
Summary: The molecular heterogeneity of cancer cells contributes to the often partial response to targeted therapies and relapse of disease due to the escape of resistant cell populations. Single-cell sequencing has limitations in understanding this heterogeneity, and scGeneRAI is an explainable deep learning approach that can infer gene regulatory networks from single-cell RNA sequencing data to provide functional insights. Our method reveals characteristic network patterns for tumor cells and normal epithelial cells and allows the reconstruction of networks at the level of single cells, which helps characterize the heterogeneity of gene regulation within and across tumors.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Aliska K. Brugmans, Carolin Walter, Natalia Moreno, Carolin Goebel, Doerthe Holdhof, Flavia W. de Faria, Marc Hotfilder, Daniela Jeising, Michael C. Fruehwald, Boris V. Skryabin, Timofey S. Rozhdestvensky, Lydia Wachsmuth, Cornelius Faber, Martin Dugas, Julian Varghese, Ulrich Schueller, Thomas K. Albert, Kornelius Kerl
Summary: Researchers have established a new mouse model to study the impact of specific non-truncating mutations in the Smarcb1 gene on brain development. Using magnetic resonance imaging, histology, and single-cell RNA sequencing, they found that these mutations disrupt neuronal development in newborn mice, affecting their weight gain and leading to enlarged brain ventricles.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Review
Genetics & Heredity
Dylan Pelletier, Barbara Rivera, Marc R. Fabian, William D. Foulkes
Summary: MicroRNAs (miRNAs) are crucial for gene expression regulation, and their biogenesis depends on specific genes such as DROSHA, DGCR8, DICER1, and AGO1/2. Germline pathogenic variants (GPVs) in these genes lead to different genetic syndromes with diverse clinical manifestations. DICER1 GPVs are associated with tumor predisposition, while recent studies have shed light on the clinical consequences of GPVs in DGCR8, AGO1, and AGO2. This review provides an up-to-date summary on how GPVs in miRNA biogenesis genes affect miRNA biology and contribute to clinical manifestations.
TRENDS IN GENETICS
(2023)
Article
Anatomy & Morphology
Xiu Qing Wang, Basile Tessier-Cloutier, Jessica Saunders, Melissa Harvey, Linlea Armstrong, Tony Ng, Christopher Dunham, Jonathan W. Bush
Summary: Pediatric CNS tumors have seen improved diagnostic accuracy with the use of immunohistochemistry and molecular techniques. The inactivation of SWI/SNF proteins, specifically INI1 and BRG1, has been found to be useful in diagnosing atypical teratoid/rhabdoid tumors. This study explored the immunohistochemical expression profile of SWI/SNF subunits and Nestin, confirming the utility of BRG1 IHC in the diagnosis of pediatric CNS tumors.
APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
(2023)
Article
Neurosciences
Matthew Pun, Drew Pratt, Patricia R. Nano, Piyush K. Joshi, Li Jiang, Bernhard Englinger, Arvind Rao, Marcin Cieslik, Arul M. Chinnaiyan, Kenneth Aldape, Stefan Pfister, Mariella G. Filbin, Aparna Bhaduri, Sriram Venneti
Summary: Globally decreased H3K27me3 is a characteristic feature of H3K27-altered DMGs and PFAs. H3K27-altered DMGs are characterized by H3K27M mutations, while most PFAs overexpress EZHIP, which shares similarity with mutant H3K27M. H3K27M and EZHIP both inhibit the function of PRC2, responsible for H3K27me3 deposition.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Dylan Pelletier, Anne-Laure Chong, Mona Wu, Leora Witkowski, Sophie Albert, Nelly Sabbaghian, Marc R. Fabian, William D. Foulkes
Summary: The endoribonuclease DICER1 is crucial in microRNA biogenesis, generating mature single-stranded miRNAs by cleaving pre-miRNA stem-loops. Pathogenic variants in DICER1 result in DICER1 tumor predisposition syndrome (DTPS), a childhood-onset tumor susceptibility disorder. Germline DICER1 missense variants in the Platform domain have been found in patients with tumors associated with DTPS, which impair miRNA biogenesis by preventing DICER1 from producing mature miRNAs and binding to pre-miRNA stem-loops.
Review
Oncology
Claire Freycon, Philip J. Lupo, Leora Witkowski, Crystal Budd, William D. Foulkes, Catherine Goudie
Summary: This systematic review found that some patients with FOXO1 fusion-positive ARMS have pathogenic/likely pathogenic variants in cancer predisposing genes, but the causal relationship between CPS and FP-ARMS could not be determined. Only one patient was diagnosed with a cancer predisposition syndrome known to be associated with rhabdomyosarcoma. Clinicians cannot solely rely on FOXO1 fusion status to distinguish patients with/without CPS.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Neurosciences
Carolin Goebel, Shweta Godbole, Melanie Schoof, Doerthe Holdhof, Catena Kresbach, Carolin Loose, Julia Neumann, Ulrich Schueller
Summary: This study demonstrates the important role of SMARCA4 deficiency in the development of Group 3 medulloblastoma and provides insights into the deregulated gene expression involved in SMARCA4/MYC-driven tumorigenesis.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Chemistry, Analytical
Georgina D. Barnabas, Verena Goebeler, Janice Tsui, Jonathan W. Bush, Philipp F. Lange
Summary: Formalin-fixed, paraffin-embedded (FFPE) tissues are valuable for retrospective studies, but their protein extraction and processing for mass spectrometry (MS) analysis are challenging. To address this, an optimized workflow called ASAP was developed for efficient protein extraction from FFPE sections without using sonicators. ASAP demonstrated high-quality data with increased proteome coverage and reproducibility in analyzing archived pediatric tumor FFPE specimens. It offers a streamlined, time- and cost-effective pipeline for high-throughput FFPE proteomics in clinical specimens.
ANALYTICAL CHEMISTRY
(2023)