Article
Genetics & Heredity
Kami Ahmad, Steven Henikoff
Summary: The study demonstrates the crucial role of chromatin silencing in cell reprogramming, with histone mutations potentially leading to unstable cell fates and cancer development. Expression of specific factors and mutant histones showed that blocking chromatin silencing can result in overgrowth of tissues resembling cancer phenotypes, highlighting the importance of proper silencing in maintaining tissue homeostasis.
Article
Oncology
Andria Rakotomalala, Quentin Bailleul, Clara Savary, Melanie Arcicasa, Maud Hamadou, Paul Huchede, Audrey Hochart, Audrey Restouin, Remy Castellano, Yves Collette, Emma Dieny, Audrey Vincent, Pierre-Olivier Angrand, Xuefen Le Bourhis, Pierre Leblond, Alessandro Furlan, Marie Castets, Eddy Pasquier, Samuel Meignan
Summary: The H3.3K27M mutation increases cell radioresistance capabilities and modulates responses to different classes of compounds in pediatric glioma cells. Besides its tumorigenic role, this mutation alters the response to treatments of pediatric glioma cells.
Article
Oncology
Yan Mo, Shoufu Duan, Xu Zhang, Xu Hua, Hui Zhou, Hong-Jian Wei, Jun Watanabe, Nicholas McQuillan, Zhenyi Su, Wei Gu, Cheng-Chia Wu, Christopher R. Vakoc, Rintaro Hashizume, Kenneth Chang, Zhiguo Zhang
Summary: The catalytic subunit of the SWI/SNF chromatin remodeling complex, SMARCA4, is essential for the proliferation and growth of diffuse midline gliomas with H3K27M mutation. This discovery provides a potential therapeutic approach to this deadly pediatric glioma.
Review
Biochemistry & Molecular Biology
Lina-Marie Briu, Chrystelle Maric, Jean-Charles Cadoret
Summary: The replication-timing program is crucial in eukaryotic nuclear processes and is closely linked to transcriptional activity, epigenetic landscape, and the 3D organization of the genome. There is a complex relationship between replication timing, replication stress, and genomic instability, although the extent of their mutual connection requires further investigation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jiho Park, Song Y. Yeu, Sangjin Paik, Hyungmin Kim, Si-Young Choi, Junyeop Lee, Jinho Jang, Semin Lee, Youngil Koh, Hyunsook Lee
Summary: Loss of BubR1 acetylation leads to chromosomal rearrangement and genetic instability in mice, with replication stress playing a key role in these processes. Moreover, defects in BubR1 acetylation in mitosis contribute to tumorigenesis, as observed in human cancer cells with whole-arm translocations demonstrating similar defects.
Review
Immunology
Payal Aggarwal, Wen Luo, Katherine C. C. Pehlivan, Hai Hoang, Prajwal Rajappa, Timothy P. P. Cripe, Kevin A. A. Cassady, Dean A. A. Lee, Mitchell S. S. Cairo
Summary: This article examines the differences and similarities between high grade gliomas in adults and children, including epidemiology, etiology, pathogenesis, and treatment approaches. Although there are differences in clinical presentation, molecular biology background, and response to chemotherapy, both types of gliomas respond to immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Rafaela Fagundes, Leonardo K. Teixeira
Summary: DNA replication must be precisely controlled, and cell cycle transitions are regulated by the Cyclin-Dependent Kinases (CDKs) family. The Cyclin E/CDK2 complex controls cell cycle progression and DNA replication through phosphorylation of specific substrates in normal cycles, while its oncogenic activation causes replication stress and genomic instability.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Oncology
Ken-ichi Yoshioka, Yusuke Matsuno
Summary: This manuscript reviews the factors that increase the risk of genomic destabilization, including the cellular state that resembles senescence, and explores the pathways leading to this instability and associated mutagenesis, ultimately resulting in cancer development.
Article
Biology
Yoichiro Harada, Yu Mizote, Takehiro Suzuki, Akiyoshi Hirayama, Satsuki Ikeda, Mikako Nishida, Toru Hiratsuka, Ayaka Ueda, Yusuke Imagawa, Kento Maeda, Yuki Ohkawa, Junko Murai, Hudson H. Freeze, Eiji Miyoshi, Shigeki Higashiyama, Heiichiro Udono, Naoshi Dohmae, Hideaki Tahara, Naoyuki Taniguchi
Summary: Mannose has anticancer activity by regulating cell metabolism and inducing dNTP loss, affecting cell cycle and chemotherapy efficacy.
Article
Genetics & Heredity
Jinxuan Xie, Yi Lin, Yajie Li, Aizhong Fang, Xin Li, Songlin Wang, Wenbin Li
Summary: This study investigates the role of TRHDE-AS1 in glioma using bioinformatic methods. It was found that TRHDE-AS1 is associated with tumor prognosis and shows significant differences in expression levels in different types of glioma. Functional analysis suggests that TRHDE-AS1 may be involved in the regulation of synapse-related functions and is significantly correlated with the expression levels of multiple cancer driver genes. Differences in TP53 and CIC gene mutations were also observed in low-grade gliomas. Furthermore, TRHDE-AS1 is correlated with various immune cells in the glioma immune microenvironment. These findings suggest that TRHDE-AS1 is involved in the development of glioma and can serve as a biomarker for predicting prognosis.
Review
Biochemistry & Molecular Biology
Veronica Marabitti, Pasquale Valenzisi, Giorgia Lillo, Eva Malacaria, Valentina Palermo, Pietro Pichierri, Annapaola Franchitto
Summary: Maintenance of genome stability is crucial for cell survival, which relies on accurate DNA replication. Transcription poses as a major threat to DNA replication, as collisions between the two processes occur frequently. R-loops, which consist of a DNA-RNA hybrid and displaced single-stranded DNA, are the main harmful structures associated with transcription. When their homeostasis is disturbed, R-loops become a potent source of replication stress and genome instability, leading to various human diseases including cancer. Cells have evolved multiple mechanisms to combat the deleterious consequences of R-loop persistence, and several replication fork protection factors have been implicated in preventing/removing these harmful structures.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Ke Zhang, Yang Sui, Wu-Long Li, Gen Chen, Xue-Chang Wu, Robert J. Kokoska, Thomas D. Petes, Dao-Qiong Zheng
Summary: The deficiency of Pol epsilon leads to genomic instability and multiple human diseases. Low levels of Pol epsilon result in cellular changes such as elevated rates of recombination, aneuploidy, contraction of ribosomal DNA repeats, shortened telomeres, increased break-induced replication, and higher rate of single-base mutations. Compared to other replicative DNA polymerases, Pol epsilon displays distinct patterns of genomic alterations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Muhammad Jameel Mughal, Kin Iong Chan, Ravikiran Mahadevappa, Sin Wa Wong, Kit Cheng Wai, Hang Fai Kwok
Summary: The study revealed a significant association between MCM10 and the clinical aggressiveness of breast cancer patients. Overexpression of MCM10 was found to promote breast cancer progression and genomic instability.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Pediatrics
Cheng Chen, JianTao Jiang, ShaoLing Fu, Cheng Wang, Yan Su, GuoHua Mei, JianFeng Xue, Jian Zou, XueQian Li, ZhongMin Shi
Summary: The HyProCure procedure showed satisfactory therapeutic effects for pediatric flexible flatfoot with a low complication rate, while implant depth was associated with postoperative outcomes.
FRONTIERS IN PEDIATRICS
(2022)
Article
Multidisciplinary Sciences
Shenglun Li, Yujia Chen, Yuduo Guo, Jiacheng Xu, Xiang Wang, Weihai Ning, Lixin Ma, Yanming Qu, Mingshan Zhang, Hongwei Zhang
Summary: This study identifies a signature of 17 lncRNAs related to genomic instability, which has prognostic value for gliomas and could potentially provide a therapeutic method for glioblastoma.
Article
Biochemistry & Molecular Biology
Laura Tovini, Sarah C. Johnson, Molly A. Guscott, Alexander M. Andersen, Diana Carolina Johanna Spierings, Rene Wardenaar, Floris Foijer, Sarah E. McClelland
Summary: Cancer cells exhibit persistent chromosomal instability, with different tumor types showing characteristic subsets of aneuploidies. Researchers used dCas9 as a carrier to recruit the kinetochore-nucleating domain of CENP-T protein to ectopically assemble kinetochores near specific genomic loci, resulting in increased chromosome instability and partial aneuploidies of target chromosomes in various cell types. The study also analyzed potential endogenous repeats that could support ectopic kinetochore formation.
Article
Biochemistry & Molecular Biology
My Anh Truong, Paula Cane-Gasull, Sippe G. de Vries, Wilco Nijenhuis, Rene Wardenaar, Lukas C. Kapitein, Floris Foijer, Susanne M. A. Lens
Summary: Various cancer types exhibit characteristic and recurrent aneuploidy patterns. The origins of these cancer type-specific karyotypes are still unknown, partly because introducing or eliminating specific chromosomes in human cells still poses a challenge. Here, we describe a novel strategy to induce mis-segregation of specific chromosomes in different human cell types. Our kinesin-based strategy opens the possibility to investigate the immediate cellular responses to specific aneuploidies in different cell types; an important step toward understanding how tissue-specific aneuploidy patterns evolve.
Article
Oncology
Andra S. Martinikova, Miroslav Stoyanov, Anna Oravetzova, Yannick P. Kok, Shibo Yu, Jana Dobrovolna, Pavel Janscak, Marcel van Vugt, Libor Macurek
Summary: Oncogene-induced replication stress is a major cause of genome instability in cancer cells. This study reveals that increased activity of PPM1D exacerbates replication stress caused by cyclin E1 overexpression, leading to abnormal cell cycle progression and accumulation of DNA copy number alterations. Pharmacological inhibition of PPM1D can alleviate replication stress-induced genome instability.
MOLECULAR ONCOLOGY
(2024)
Article
Multidisciplinary Sciences
Lorenza Garribba, Giuseppina De Feudis, Valentino Martis, Martina Galli, Marie Dumont, Yonatan Eliezer, Rene Wardenaar, Marica Rosaria Ippolito, Divya Ramalingam Iyer, Andrea E. Tijhuis, Diana C. J. Spierings, Michael Schubert, Silvia Taglietti, Chiara Soriani, Simon Gemble, Renata Basto, Nick Rhind, Floris Foijer, Uri Ben-David, Daniele Fachinetti, Ylli Doksani, Stefano Santaguida
Summary: Chromosomal instability (CIN) is a common form of genome instability and is closely associated with cancer. Aneuploidy, a state of karyotype imbalance, can trigger CIN and result in genetically diverse cells with chromosomal abnormalities. Cycling aneuploid cells have lower karyotype complexity compared to arrested ones, but both show increased expression of DNA repair signatures. Interestingly, highly-proliferative cancer cells also exhibit upregulation of the same signatures, which allows them to proliferate despite aneuploidy-induced CIN.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Eleanor L. Woodward, Minjun Yang, Larissa H. Moura-Castro, Hilda van den Bos, Rebeqa Gunnarsson, Linda Olsson-Arvidsson, Diana C. J. Spierings, Anders Castor, Nicolas Duployez, Marketa Zaliova, Jan Zuna, Bertil Johansson, Floris Foijer, Kajsa Paulsson
Summary: This study reveals that the aneuploidies in high hyperdiploid acute lymphoblastic leukemia (HeH ALL) may originate early and follow a punctuated evolution process, using single-cell whole genome sequencing and in silico modeling.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Lavinia Spain, Alexander Coulton, Irene Lobon, Andrew Rowan, Desiree Schnidrig, Scott T. C. Shepherd, Benjamin Shum, Fiona Byrne, Maria Goicoechea, Elisa Piperni, Lewis Au, Kim Edmonds, Eleanor Carlyle, Nikki Hunter, Alexandra Renn, Christina Messiou, Peta Hughes, Jaime Nobbs, Floris Foijer, Hilda van den Bos, Rene Wardenaar, Diana C. J. Spierings, Charlotte Spencer, Andreas M. Schmitt, Zayd Tippu, Karla Lingard, Lauren Grostate, Kema Peat, Kayleigh Kelly, Sarah Sarker, Sarah Vaughan, Mary Mangwende, Lauren Terry, Denise Kelly, Jennifer Biano, Aida Murra, Justine Korteweg, Charlotte Lewis, Molly O'Flaherty, Anne-Laure Cattin, Max Emmerich, Camille L. Gerard, Husayn Ahmed Pallikonda, Joanna Lynch, Robert Mason, Aljosja Rogiers, Hang Xu, Ariana Huebner, Nicholas McGranahan, Maise Al Bakir, Jun Murai, Cristina Naceur-Lombardelli, Elaine Borg, Miriam Mitchison, David A. Moore, Mary Falzon, Ian Proctor, Gordon W. H. Stamp, Emma L. Nye, Kate Young, Andrew J. S. Furness, Lisa Pickering, Ruby Stewart, Ula Mahadeva, Anna Green, James Larkin, Kevin Litchfield, Charles Swanton, Mariam Jamal-Hanjani, Samra Turajlic
Summary: Understanding the evolutionary pathways and resistance mechanisms of melanoma is crucial for improving outcomes. This study provides a comprehensive analysis of advanced melanoma, revealing the diverse strategies used by melanoma to evade treatment and the immune system.
Article
Biology
Esther Stroo, Leen Janssen, Olga Sin, Wytse Hogewerf, Mirjam Koster, Liesbeth Harkema, Sameh A. Youssef, Natalie Beschorner, Anouk H. G. Wolters, Bjorn Bakker, Lore Becker, Lilian Garrett, Susan Marschall, Sabine M. Hoelter, Wolfgang Wurst, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe de Angelis, Amanth Thathiah, Floris Foijer, Bart van de Sluis, Jan van Deursen, Matthias Jucker, Alain de Brun, Ellen A. A. Nollen
Summary: In age-related neurodegenerative diseases, disease-specific proteins form amyloid-like deposits. Depletion of SERF proteins can ameliorate this process. However, it is unknown whether SERF modifies amyloid pathology in mammalian brain.
LIFE SCIENCE ALLIANCE
(2023)
Article
Cell Biology
Colin Stok, Stavroula Tsaridou, Nathalie van den Tempel, Marieke Everts, Elles Wierenga, Femke J. Bakker, Yannick Kok, Ines Teles Alves, Lucas T. Jae, Maximilian W. D. Raas, Pim J. Huis in't Veld, H. Rudolf de Boer, Arkajyoti Bhattacharya, Eleftheria Karanika, Harry Warner, Mengting Chen, Bert van de Kooij, Julien Dessapt, Lars ter Morsche, Polina Perepelkina, Amelie Fradet-Turcotte, Victor Guryev, Eelco C. Tromer, Kok-Lung Chan, Rudolf S. N. Fehrmann, Marcel A. T. M. van Vugt
Summary: Joint DNA molecules are byproducts of DNA replication and repair. Persistent joint molecules form ultrafine DNA bridges (UFBs) in mitosis, affecting sister chromatid separation. PICH plays a central role in resolving UFBs. A loss-of-function screen reveals that FIRRM interacts with and stabilizes FIGNL1, and their inactivation leads to UFB formation, RAD51 accumulation, impaired replication fork dynamics, and genome instability. These findings suggest that dysregulation of RAD51 dynamics at replication forks due to FIRRM and FIGNL1 inactivation results in persistent DNA lesions and a dependence on PICH for cell survival.
Review
Biochemistry & Molecular Biology
Anouk van den Brink, Maria F. Suarez Peredo F. Rodriguez, Floris Foijer
Summary: Chromosomal instability (CIN) leads to increased chromosomal segregation abnormalities, causing intratumor heterogeneity in most human cancers. CIN can result in mislocalized micronuclei in the cytoplasm, which can be detected by cGAS, leading to an inflammatory response and immune cell activation. The molecular network underlying the CIN-induced inflammatory response is not well understood, and there is emerging evidence that some cancers avoid this immune response. The STAT1, STAT3, and NF-κB signaling cascades are important in the CIN-induced inflammatory response.
CHROMOSOME RESEARCH
(2023)
Article
Cell & Tissue Engineering
Amanda Faria Assoni, Floris Foijer, Mayana Zatz
Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects the motor system and is caused by multiple pathogenic processes. The Fused in Sarcoma (FUS) gene is associated with ALS6 and plays a role in the impaired cellular functions of degenerating motor neurons. The localization of FUS and protein synthesis rates could be potential therapeutic targets for ALS.
STEM CELL REVIEWS AND REPORTS
(2023)
Article
Multidisciplinary Sciences
Amanda Faria Assoni, Thiago Giove Mitsugi, Rene Wardenaar, Raiane Oliveira Ferreira, Elisa Helena Farias Jandrey, Gabriela Machado Novaes, Isabela Fonseca de Oliveira Granha, Petra Bakker, Carolini Kaid, Mayana Zatz, Floris Foijer, Oswaldo Keith Okamoto
Summary: This study found that high expression of VAPB in medulloblastoma is associated with decreased patient survival, and VAPB is required for normal proliferation of medulloblastoma cells.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Karim H. Saba, Valeria Difilippo, Michal Kovac, Louise Cornmark, Linda Magnusson, Jenny Nilsson, Hilda van den Bos, Diana C. J. Spierings, Mahtab Bidgoli, Tord Jonson, Vaiyapuri P. Sumathi, Otte Brosjoe, Johan Staaf, Floris Foijer, Emelie Styring, Michaela Nathrath, Daniel Baumhoer, Karolin H. Nord
Summary: TP53 is a frequently mutated gene in human cancer. In the study of osteosarcoma, a primary bone malignancy, it was found that TP53 structural variants commonly result in loss of coding parts of the gene while simultaneously preserving and relocating the promoter region. The transferred TP53 promoter region is fused to genes previously implicated in cancer development, and paradoxically, these upregulated genes are significantly associated with the TP53 signalling pathway itself.
JOURNAL OF PATHOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Nadeem Shaikh, Alice Mazzagatti, Simone De Angelis, Sarah C. Johnson, Bjorn Bakker, Diana C. J. Spierings, Rene Wardenaar, Eleni Maniati, Jun Wang, Michael A. Boemo, Floris Foijer, Sarah E. McClelland
Summary: The study identified various types of DNA copy number alterations (CNAs) caused by replication stress induced by aphidicolin or hydroxyurea in single, diploid non-transformed cells. Different types of CNAs were associated with distinct genomic regions and features, and the CNAs induced by aphidicolin and hydroxyurea were found to have unique patterns. The research highlights the impact of replication stress on chromosomal instability and provides insights into the molecular mechanisms driving cancer evolution.