Article
Clinical Neurology
Philipp Sievers, Martin Sill, Christina Blume, Arnault Tauziede-Espariat, Daniel Schrimpf, Damian Stichel, David E. Reuss, Helin Dogan, Christian Hartmann, Christian Mawrin, Martin Hasselblatt, Walter Stummer, Uta Schick, Jurgen Hench, Stephan Frank, Ralf Ketter, Leonille Schweizer, Jens Schittenhelm, Stephanie Puget, Sebastian Brandner, Zane Jaunmuktane, Benno Kusters, Zied Abdullaev, Melike Pekmezci, Matija Snuderl, Miriam Ratliff, Christel Herold-Mende, Andreas Unterberg, Kenneth Aldape, David W. Ellison, Pieter Wesseling, Guido Reifenberger, Wolfgang Wick, Arie Perry, Pascale Varlet, Stefan M. Pfister, David T. W. Jones, Andreas von Deimling, Felix Sahm
Summary: The study explores the molecular characteristics of clear cell meningioma, revealing a distinct epigenetic signature and recurrent mutations in the SMARCE1 gene. Patients with clear cell meningioma show a similar prognosis to those with meningioma WHO grade 2, supporting the classification of these tumors as WHO grade 2.
ACTA NEUROPATHOLOGICA
(2021)
Article
Biochemistry & Molecular Biology
Chunming Dong, Rui Zhang, Lijun Xu, Beibei Liu, Xinlei Chu
Summary: This study investigates the assembly mechanism and structure of the multi-subunit ATP-dependent chromatin remodeling factor SWI/SNF complex, as well as the interactions between its subunits. Experimental results demonstrate the assembly mechanism of the core subunit quaternary complexes of the BAF complex and provide crystal structures of corresponding binary complexes. This study provides a theoretical basis for cancer and drug research based on protein structure.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Oncology
Serena Ammendola, Michele Simbolo, Chiara Ciaparrone, Paola Chiara Rizzo, Maria Caffo, Giampietro Pinna, Francesco Sala, Aldo Scarpa, Valeria Barresi
Summary: Intraventricular meningiomas are rare brain tumors with potentially life-threatening complications during surgical resection. This study characterizes the molecular profile of these tumors and identifies NF2 mutation as a recurring alteration. These findings provide potential therapeutic targets for the treatment of these tumors.
Article
Genetics & Heredity
Alireza Shoakazemi, Alan Hewitt, Miriam J. Smith, Daniel du Plessis, Owen Thomas, Stavros M. Stivaros, Kenan Deniz, Charlotte Hammerbeck-ward, Scott A. Rutherford, Andrew Thomas King, D. Gareth Evans
Summary: Clear cell meningioma (CCM) is a rare variant associated with SMARCE1 gene mutations. Genetic counseling and regular brain/spine imaging screening are important for family members of patients with SMARCE1 pathogenic variants to detect tumors early.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Oncology
Katharina Pries, Sandra Krueger, Steffen Heckl, Hans-Michael Behrens, Christoph Roecken
Summary: Recent studies have found a connection between certain subunits of the SWI/SNF complex and specific tumor characteristics in gastric cancer. This study aimed to examine the expression patterns of SMARCA4 and SMARCE1, two subunits of the SWI/SNF complex, in gastric cancer and their potential relationship with ERBB2. The results showed significant correlations between the expressions of SMARCA4 and SMARCE1 with ARID1A, p53, and microsatellite status, but not with patient prognosis. Amplification analysis revealed co-amplification of SMARCE1 and ERBB2 in some cases, suggesting potential synergistic effects for improved treatment of gastric cancer.
Article
Biochemistry & Molecular Biology
Xiaosong Hu, Ruochen Liu, Jianbing Hou, Wen Peng, Sicheng Wan, Minghao Xu, Yongsen Li, Guanghui Zhang, Xuan Zhai, Ping Liang, Hongjuan Cui
Summary: This study reveals the critical oncogenic role of SMARCE1 gene in neuroblastoma, particularly in cases with MYCN amplification. SMARCE1 interacts with MYCN to mediate transcriptional activation of downstream target genes, promoting neuroblastoma proliferation and tumorigenicity. These findings provide a new potential therapeutic target for neuroblastoma with 17q21-ter gain and MYCN amplification.
Article
Biotechnology & Applied Microbiology
Elizabeth M. Boazak, Rebecca King, Jiaxing Wang, Cassandra M. Chu, Aaron M. Toporek, Joseph M. Sherwood, Darryl R. Overby, Eldon E. Geisert, C. Ross Ethier
Summary: This study identified genes potentially regulating biomechanical tissue properties of the cornea and sclera by conducting ocular compliance measurements in BXD mice, and highlighted Smarce1 and Tns4 as candidate genes that may influence the development and regulation of tissue material properties. Further research on these genes is encouraged for understanding ocular pathologies and developing novel mouse models of eye diseases like myopia and glaucoma.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Genetics & Heredity
Erika Fiorentini, Laura Giunti, Andrea Di Rita, Simone Peraio, Carla Fonte, Chiara Caporalini, Anna Maria Buccoliero, Maria Luigia Censullo, Giulia Gori, Alice Noris, Rosa Pasquariello, Roberta Battini, Rossana Pavone, Flavio Giordano, Sabrina Giglio, Berardo Rinaldi
Summary: We present a case of a 16-year-old girl with spinal clear-cell multiple meningiomas (CCMs). Genetic testing identified a germline heterozygous variant in SMARCE1, and further investigations confirmed its causative role. This case highlights the importance of next-generation sequencing (NGS) in identifying predisposing genes for meningiomas, particularly in pediatric CCM patients. It also emphasizes the need for molecular assessment and specific screening follow-up for carriers of pathogenic variants in SMARCE1.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
Roodolph St Pierre, Clayton K. Collings, Daniel D. Same Guerra, Christian J. Widmer, Olubusayo Bolonduro, Nazar Mashtalir, Akshay Sankar, Yu Liang, Wenya Linda Bi, Erica H. Gerkes, Vijaya Ramesh, Jun Qi, Miriam J. Smith, David M. Meredith, Cigall Kadoch
Summary: SMARCE1 loss destabilizes the canonical BAF complex and increases the formation of BRD9-containing non-canonical (ncBAF) complexes. This study reveals a structural role for SMARCE1 in stabilizing the canonical BAF complex on chromatin and identifies potential therapeutic approaches for SMARCE1-deficient clear cell meningioma tumors.
Article
Multidisciplinary Sciences
Zhengyu Qian, Jingwei Ye, Jinteng Li, Yunshu Che, Wenhui Yu, Peitao Xu, Jiajie Lin, Feng Ye, Xiaojun Xu, Zepeng Su, Dateng Li, Zhongyu Xie, Yanfeng Wu, Huiyong Shen
Summary: This study aimed to explore the role of crotonylation in myogenic differentiation and its potential as a target in myogenic dysfunction diseases. Through in vitro and in vivo experiments, it was confirmed that crotonylation affects muscle differentiation and the crotonylation eraser HDAC3 regulates myogenic differentiation. The findings contribute to a better understanding of the pathophysiological processes of muscle injury repair and sarcopenia.
JOURNAL OF ADVANCED RESEARCH
(2023)
Article
Oncology
Simon Haefliger, Olga Chervova, Christopher Davies, Steven Nottley, Steven Hargreaves, Vaiyapuri P. Sumathi, Fernanda Amary, Roberto Tirabosco, Nischalan Pillay, Stephan Beck, Adrienne M. Flanagan, Iben Lyskjaer
Summary: Epithelioid sarcoma is a rare and aggressive tumor characterized by the loss of SMARCB1 expression. Limited research attention and therapeutic options exist for this disease. Methylation profiling helps distinguish epithelioid sarcoma from other tumors, and immunotherapy may be a promising treatment strategy.
JOURNAL OF PATHOLOGY
(2023)
Article
Cell Biology
Hwajung Choi, Liu Yang, Yudong Liu, Ju-Kyung Jeong, Eui-Sic Cho
Summary: In this study, the factors and mechanisms of tooth root resorption were investigated using transgenic mice. It was found that cementum thickness and signaling pathways are associated with tooth root resorption. Dickkopf-related protein 1 was identified as a key molecule in the process of tooth root resorption. The study suggests that proper function and sustained signaling are crucial for tooth root homeostasis.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Review
Oncology
Vincenzo Di Nunno, Caterina Giannini, Sofia Asioli, Alfredo Conti, Julia Furtner, Damiano Balestrini, Alicia Tosoni
Summary: Only 1% of meningioma cases are classified as malignant (anaplastic) meningioma. Due to their rarity, there are gaps in the clinical management of these tumors. This review investigates the current knowledge of anaplastic meningioma in terms of pathological and radiological diagnosis, molecular assessment, and treatment approaches. Surgery and radiation therapy play a crucial role in managing grade 3 meningioma, while systemic therapy is not widely used. It is anticipated that the increasing understanding of molecular pathways will lead to the development of more effective systemic treatments.
Article
Multidisciplinary Sciences
Tenghan Zhuang, Boyan Zhang, Yihong Song, Fan Huang, Wangfei Chi, Guangwei Xin, Ziyu Zhang, Steven Y. Cheng, Qing Jiang, Chuanmao Zhang
Summary: Sufu, as a negative regulator, plays a critical role in both centrosome and nuclear localization, regulating centrosome duplication and DNA replication by facilitating CP110 phosphorylation and Cdt1 degradation. Serum stimulation leads to the removal of Sufu from the centrosome and nucleus, promoting cell cycle progression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Genetics & Heredity
Scott R. Plotkin, Ludwine Messiaen, Eric Legius, Patrice Pancza, Robert A. Avery, Jaishri O. Blakeley, Dusica Babovic-Vuksanovic, Rosalie Ferner, Michael J. Fisher, Jan M. Friedman, Marco Giovannini, David H. Gutmann, Clemens Oliver Hanemann, Michel Kalamarides, Hildegard Kehrer-Sawatzki, Bruce R. Korf, Victor-Felix Mautner, Mia MacCollin, Laura Papi, Katherine A. Rauen, Vincent Riccardi, Elizabeth Schorry, Miriam J. Smith, Anat Stemmer-Rachamimov, David A. Stevenson, Nicole J. Ullrich, David Viskochil, Katharina Wimmer, Kaleb Yohay, Susan M. Huson, Pierre Wolkenstein, D. Gareth Evans
Summary: The study aims to update the diagnostic criteria for neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) by incorporating recent advances in genetics, ophthalmology, neuropathology, and neuroimaging. The updated criteria include clinical features and genetic testing, emphasizing the phenotypic overlap between the two conditions.
GENETICS IN MEDICINE
(2022)
Article
Oncology
Elke M. van Veen, D. Gareth Evans, Elaine F. Harkness, Helen J. Byers, Jamie M. Ellingford, Emma R. Woodward, Naomi L. Bowers, Andrew J. Wallace, Sacha J. Howell, Anthony Howell, Fiona Lalloo, William G. Newman, Miriam J. Smith
Summary: The study found that in women with lobular breast cancer, pathogenic germline variants in genes other than BRCA1/2, such as ATM, also significantly increase the risk of the disease. Extended panel genetic testing can help improve early risk identification and intervention.
Article
Genetics & Heredity
D. Gareth Evans, Elke Maria van Veen, Helen J. Byers, Sarah J. Evans, George J. Burghel, Emma Roisin Woodward, Elaine F. Harkness, Diana M. Eccles, Stephanie L. Greville-Haygate, Jamie M. Ellingford, Naomi L. Bowers, Marta Pereira, Andrew J. Wallace, Sasha J. Howell, Anthony Howell, Fiona Lalloo, William G. Newman, Miriam Jane Smith
Summary: The study shows that the rates of BRCA1, BRCA2, and TP53 PVs are high in very early onset breast cancer cases. Testing of additional breast cancer-associated genes did not provide significant benefits. BRCA1/2 PVs were more common in women aged 26-30 years compared to younger women, and the younger age group had rates similar to other study cohorts.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Oncology
Miriam J. Smith, D. Gareth Evans
Summary: Upon evaluating 21 PTCH1/SUFU negative GS families, no pathogenic PTCH2 variants were identified, nor could previously published PTCH2 variants be considered pathogenic based on current guidelines. The absence of clear pathogenic variants in GS families and the high frequency of LoF variants in the general population suggest PTCH2 should not be included in panels for genetic diagnosis of GS.
Article
Genetics & Heredity
Nicola Flaum, Elke M. van Veen, Olivia Smith, Stephanie Amico, William G. Newman, Emma J. Crosbie, Richard Edmondson, Miriam J. Smith, D. Gareth Evans
Summary: BRIP1 gene variants are associated with the risk of breast cancer and/or ovarian cancer, with the c.1045G>C variant showing a higher risk, especially for women with EOC. The study underscores the importance of BRIP1 as an EOC susceptibility gene, particularly in familial cases.
Article
Genetics & Heredity
Fanxuan Deng, D. Gareth Evans, Miriam J. Smith
Summary: Schwannomatosis is a rare tumor predisposition syndrome that is difficult to classify and interpret the clinical significance of novel variants. Current classification guidelines can accurately identify most pathogenic variants, but there is a high frequency of LoF LZTR1 variants in the general population, making classification of novel variants challenging.
Article
Genetics & Heredity
Lea Guerrini-Rousseau, Julien Masliah-Planchon, Sebastian M. Waszak, Pia Alhopuro, Patrick R. Benusiglio, Franck Bourdeaut, Ines B. Brecht, Giada Del Baldo, Sandeep Kumar Dhanda, Maria Luisa Garre, Corrie E. M. Gidding, Steffen Hirsch, Pauline Hoarau, Mette Jorgensen, Christian Kratz, Lucie Lafay-Cousin, Angela Mastronuzzi, Lorenza Pastorino, Stefan M. Pfister, Christopher Schroeder, Miriam Jane Smith, Pia Vahteristo, Roseline Vibert, Catheline Vilain, Nicolas Waespe, Ingrid M. Winship, D. Gareth Evans, Laurence Brugieres
Summary: This study found that carriers of germline SUFU pathogenic variants have a lifelong increased risk of tumors, with medulloblastoma being dominant before the age of 5, gonadal tumors during adolescence, and basal cell carcinoma and meningioma in adulthood. These findings emphasize the need for fine-tuned surveillance programs.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Genetics & Heredity
Roodolph St Pierre, Clayton K. Collings, Daniel D. Same Guerra, Christian J. Widmer, Olubusayo Bolonduro, Nazar Mashtalir, Akshay Sankar, Yu Liang, Wenya Linda Bi, Erica H. Gerkes, Vijaya Ramesh, Jun Qi, Miriam J. Smith, David M. Meredith, Cigall Kadoch
Summary: SMARCE1 loss destabilizes the canonical BAF complex and increases the formation of BRD9-containing non-canonical (ncBAF) complexes. This study reveals a structural role for SMARCE1 in stabilizing the canonical BAF complex on chromatin and identifies potential therapeutic approaches for SMARCE1-deficient clear cell meningioma tumors.
Article
Oncology
Chay Paterson, Ivana Bozic, Miriam J. Smith, Xanthe Hoad, D. Gareth R. Evans
Summary: This study presents a mechanistic approach to modeling the initiation and malignant transformation of vestibular schwannoma, resulting in new parameter estimates. The results suggest that radiotherapy may have a negligible excess risk of malignancy for sporadic vestibular schwannoma.
BRITISH JOURNAL OF CANCER
(2022)
Article
Dermatology
Yanshan Liu, Siddharth Banka, Yingzhi Huang, Jonathan Hardman-Smart, Derek Pye, Antonio Torrelo, Glenda M. Beaman, Marcelo G. Kazanietz, Martin J. Baker, Carlo Ferrazzano, Chenfu Shi, Gisela Orozco, Stephen Eyre, Michel van Geel, Anette Bygum, Judith Fischer, Zosia Miedzybrodzka, Faris Abuzahra, Albert Rubben, Sara Cuvertino, Jamie M. Ellingford, Miriam J. Smith, D. Gareth Evans, Lizelotte J. M. T. Weppner-Parren, Maurice A. M. van Steensel, Iskander H. Chaudhary, D. Chas Mangham, John T. Lear, Ralf Paus, Jorge Frank, William G. Newman, Xue Zhang
Summary: This study identifies small tandem noncoding intergenic duplications at chromosome Xq26.1 as the cause of Bazex-Dupre-Christol syndrome (BDCS). These duplications likely dysregulate the flanking centromeric gene ARHGAP36. Loss-of-function variants in ACTRT1 are unlikely to cause BDCS.
BRITISH JOURNAL OF DERMATOLOGY
(2022)
Article
Genetics & Heredity
Nicola Flaum, Emma J. Crosbie, Richard Edmondson, Emma R. Woodward, Fiona Lalloo, Miriam J. Smith, Helene Schlecht, D. Gareth Evans
Summary: This study reviewed the genetic testing of women with familial epithelial ovarian cancer (EOC) at a center. One-fifth of BRCA-negative women carried potentially actionable gene variants. Wider genetic testing of women with familial EOC is essential for optimizing treatment and preventing disease in family members.
GENETICS IN MEDICINE
(2022)
Article
Clinical Neurology
Katherine Sadler, John Bowes, Charlie F. Rowlands, Cristina Perez-Becerril, C. Mwee van der Meer, Andrew T. King, Scott A. Rutherford, Omar N. Pathmanaban, Charlotte Hammerbeck-Ward, Simon K. W. Lloyd, Simon R. Freeman, Ricky Williams, Cathal John Hannan, Daniel Lewis, Steve Eyre, D. Gareth Evans, Miriam J. Smith
Summary: A genome-wide association study revealed that rs1556516 in the 9p21.3 region is associated with the risk of vestibular schwannoma. The dysregulation of CDKN2B-AS1 and CDKN2A/B genes in this region has been linked to multiple pathologies, and these genes have been shown to influence each other's expression. The recurrent associations of the 9p21.3 region with known oncogenic pathways provide compelling evidence for its involvement in vestibular schwannoma tumorigenesis.
Article
Genetics & Heredity
D. Gareth Evans, George J. Burghel, Miriam Jane Smith
Summary: NF2-related schwannomatosis is a genetic condition that causes multiple benign tumors of the nervous system. It is caused by pathogenic variants in the NF2 gene, with six specific CpG nonsense variants being responsible for a majority of the cases. The de novo heterozygote to mosaicism ratio of one of these variants, NF2 c.586C>T; p.(Arg196Ter), is higher compared to the others, possibly due to variations in mutation rates during meiosis and mitosis.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
D. Gareth Evans, Siva Sithambaram, Elke Maria van Veen, George J. Burghel, Helene Schlecht, Elaine F. Harkness, Helen Byers, Jamie M. Ellingford, Ashu Gandhi, Sacha J. Howell, Anthony Howell, Claire Forde, Fiona Lalloo, William G. Newman, Miriam Jane Smith, Emma Roisin Woodward
Summary: This study aimed to investigate the frequency of germline pathogenic variants (PVs) in women with ductal carcinoma in situ (DCIS) and grade 1 invasive breast cancer (G1BC). The results showed that DCIS was more likely to be associated with both BRCA1/2 and non-BRCA1/2 PVs than G1BC. Extended panel testing is recommended for young-onset DCIS where PV detection rates are highest.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Oncology
Miriam J. Smith, Emma R. Woodward, D. Gareth Evans
Summary: Recent genetic sequencing studies have identified loss-of-function variants in the ELP1 and GPR161 genes as causes of childhood medulloblastoma. Although there is speculation that GPR161 may also cause Gorlin syndrome, the projected risks of developing medulloblastoma with these gene variants are relatively low and do not warrant MRI screening in infants.
Article
Genetics & Heredity
Mikey B. Lebrett, Miriam J. Smith, Emma J. Crosbie, John Bowes, Helen J. Byers, Gareth Evans, Philip A. J. Crosbie
Summary: The study investigated the performance of previously published polygenic risk scores (PRSs) for lung cancer (LC) and found that genetic variables could be used for screening selection and potentially improve screening effectiveness. Among the 9 PRSs validated in a high-risk case-control cohort, the best-performing PRS had an independent high area under the curve (AUC). Two novel loci, in the DAPK1 and MAGI2 genes, were significantly associated with LC risk. These findings suggest that PRSs may improve LC risk prediction and screening selection.
GENETICS IN MEDICINE
(2023)