Editorial Material
Multidisciplinary Sciences
Craig M. Bielski, Barry S. Taylor
Summary: Genomic instability is a characteristic of cancer, but exploiting this feature to selectively target cancer cells remains a major challenge in cancer biology with significant implications for drug development.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Lorenza Garribba, Stefano Santaguida
Summary: Proper partitioning of sister chromatids is crucial for maintaining cell stability. Errors in this process can lead to chromosome abnormalities and DNA damage, which can promote tumor growth.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Sjoerd J. Klaasen, Geert J. P. L. Kops
Summary: Aneuploidy, caused by chromosome segregation errors during cell divisions, is a significant factor in cancer and miscarriages in humans. Recent progress in understanding the prevalence and causes of non-random chromosome segregation errors has important implications for cancer and human reproduction.
Article
Cell Biology
Marianna Trakala, Muskaan Aggarwal, Courtney Sniffen, Lauren Zasadil, Allison Carroll, Duanduan Ma, Xiaofeng A. Su, Darawalee Wangsa, Ashleigh Meyer, Cynthia J. Sieben, Jian Zhong, Pei-hsin Hsu, Glenn Paradis, Thomas Ried, Andrew Holland, Jan Van Deursen, Angelika Amon
Summary: Chromosome gains and losses are common in human cancers, but how they can counteract the effects of aneuploidy remains unclear. Research using mouse models suggests that clonal selection and specific gene properties can drive cancer development.
GENES & DEVELOPMENT
(2021)
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
Matthew N. Clarke, Theodor Marsoner, Manuel Alonso Y. Adell, Madhwesh C. Ravichandran, Christopher S. Campbell
Summary: Both an increased frequency of chromosome missegregation (chromosomal instability, CIN) and the presence of an abnormal complement of chromosomes (aneuploidy) are hallmarks of cancer. We previously studied yeast cells lacking the gene BIR1, a member of the chromosomal passenger complex (CPC), and found that they quickly adapted to high levels of CIN by acquiring specific combinations of beneficial aneuploidies. In this study, we monitored these yeast strains over a longer period of time and identified suppressor mutations that reduce chromosomal instability but not the negative effects of aneuploidy.
Article
Multidisciplinary Sciences
Klaske M. Schukken, Yinan Zhu, Petra L. Bakker, Mirjam H. Koster, Liesbeth Harkema, Sameh A. Youssef, Alain de Bruin, Floris Foijer
Summary: This study induced systemic high-grade CIN in adult mice and found that it is most toxic to the high cell turnover intestinal epithelia, causing rapid villous atrophy, atypia, and apoptosis. Despite severe intestinal phenotype, most other tissues are unaffected, except for minor abnormalities in the spleen.
SCIENTIFIC REPORTS
(2021)
Review
Cell Biology
Laura J. Jilderda, Lin Zhou, Floris Foijer
Summary: Chromosomal instability leads to cells with abnormal numbers of chromosomes, which is detrimental during development and in primary cells, but is also a hallmark of cancer cells. It is believed that premalignant cells need to overcome this instability to become tumorigenic, and some aneuploidy-tolerating pathways may be therapeutically beneficial.
Article
Environmental Sciences
Miguel Santibanez-Andrade, Yesennia Sanchez-Perez, Yolanda Chirino, Rocio Morales-Barcenas, Raul Quintana-Belmares, Claudia M. Garcia-Cuellar
Summary: This study found that PM10 regulates SETD2 and SAC components in A549 lung cancer cells, leading to abnormal mitotic process and chromosomal instability.
Article
Environmental Sciences
Ana P. Ferragut Cardoso, Alexandra N. Nail, Mayukh Banerjee, Sandra S. Wise, J. Christopher States
Summary: Chronic inorganic arsenic (iAs) exposure in drinking water is a global issue affecting over 225 million people, with skin being the major target organ for iAs. Dysregulation of miRNA and chromosomal instability (CIN) are proposed mechanisms of iAs-induced carcinogenesis. This study suggests that overexpression of miR-186 contributes to iAs-induced transformation of keratinocytes by targeting mitotic regulators and inducing CIN.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Review
Oncology
Tom van den Bosch, Sarah Derks, Daniel M. Miedema
Summary: This article discusses the role of cell heterogeneity and karyotype variation in predicting the survival rate of cancer patients. Karyotype heterogeneity is driven by chromosomal instability, which in turn is influenced by both intrinsic and extrinsic selective pressures. The study also explores how chromosomal instability modulates cell phenotype and the immune microenvironment.
Review
Biochemistry & Molecular Biology
Ming Du, Shuo Zhang, Xiaoxia Liu, Congjian Xu, Xiaoyan Zhang
Summary: This article reviews the survival stresses and adaptive tolerances within nondiploid cancer cells and summarizes potential therapeutic ploidy-selective alterations, providing insights for the development of future cancer therapy.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Plant Sciences
Ruili Lv, Changyi Wang, Ruisi Wang, Xiaofei Wang, Jing Zhao, Bin Wang, Tariq Aslam, Fangpu Han, Bao Liu
Summary: Newly formed plant allopolyploids often exhibit chromosomal instability, but not all are equally unstable. This study reports a specific lineage of a relatively stable synthetic allotetraploid wheat, which shows transgenerational chromosomal instability and affects multiple phenotypic traits, particularly those related to reproductive fitness.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Multidisciplinary Sciences
G. Yahya, P. Menges, P. S. Amponsah, D. A. Ngandiri, D. Schulz, A. Wallek, N. Kulak, M. Mann, P. Cramer, V Savage, M. Raeschle, Z. Storchova
Summary: Ploidy changes are common in nature and have significant impacts on evolution, functional specialization, and tumorigenesis. This study reveals that gene expression scales allometrically with cellular ploidy, and the scaling is achieved through decreased rRNA and ribosomal protein abundance and reduced translation. The reduced activity of Tor1 with increasing ploidy leads to diminished rRNA gene repression, which is regulated by the Tor1-Sch9-Tup1 signaling pathway. The mTORC1-Sch9/S6K-Tup1/TLE1 pathway plays a crucial role in proteome remodeling in response to increased ploidy.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Jing Li, Shunya Ohmura, Aruna Marchetto, Martin F. Orth, Roland Imle, Marlene Dallmayer, Julian Musa, Maximilian M. L. Knott, Tilman L. B. Holting, Stefanie Stein, Cornelius M. Funk, Ana Sastre, Javier Alonso, Felix Bestvater, Merve Kasan, Laura Romero-Perez, Wolfgang Hartmann, Andreas Ranft, Ana Banito, Uta Dirksen, Thomas Kirchner, Florencia Cidre-Aranaz, Thomas G. P. Gruenewald
Summary: The study shows that targeting PRC1 or PLK1 can induce fatal genomic instability and tumor regression in EwS model. EWSR1-FLI1, an oncogenic transcription factor specific to EwS, hijacks PRC1 to promote tumor growth by binding to GGAA microsatellite. High PRC1 expression creates a therapeutic vulnerability towards PLK1 inhibition, leading to repression of even chemo-resistant EwS cells by triggering mitotic catastrophe.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Andrew J. C. Russell, Theo Sanderson, Ellen Bushell, Arthur M. Talman, Burcu Anar, Gareth Girling, Mirjam Hunziker, Robyn S. Kent, Julie S. Martin, Tom Metcalf, Ruddy Montandon, Vikash Pandey, Mercedes Pardo, A. Brett Roberts, Claire Sayers, Frank Schwach, Jyoti S. Choudhary, Julian C. Rayner, Thierry Voet, Katarzyna K. Modrzynska, Andrew P. Waters, Mara K. N. Lawniczak, Oliver Billker
Summary: Malaria transmission to mosquitoes requires a developmental switch in parasites. The transcription factor AP2-G is essential for this switch. The determination of the parasite's sex and its subsequent differentiation are regulated by a cascade of gene functions. Germ-granule-like ribonucleoprotein complexes complement transcriptional processes in the regulation of both male and female development of the parasite.
CELL HOST & MICROBE
(2023)
Article
Obstetrics & Gynecology
Olga Tsuiko, Yasmine El Ayeb, Tatjana Jatsenko, Joke Allemeersch, Cindy Melotte, Jia Ding, Sophie Debrock, Karen Peeraer, Arne Vanhie, Anne De Leener, Celine Pirard, Candice Kluyskens, Ellen Denayer, Eric Legius, Joris Robert Vermeesch, Hilde Brems, Eftychia Dimitriadou
Summary: Long-read amplicon sequencing is a simple and cost-effective strategy for preclinical preimplantation genetic testing in couples with a de novo pathogenic variant. This approach allows for the identification of the parental origin of the mutant allele and provides access to universal genome-wide haplotyping-based PGT programs. The success rate of this method is 75%.
HUMAN REPRODUCTION
(2023)
Article
Ethics
Zoe Claesen, Neeltje Crombag, Lidewij Henneman, Joris Robert Vermeesch, Pascal Borry
Summary: In this paper, the authors evaluate the role of the child's right to an open future in setting the scope of non-invasive prenatal testing (NIPT). They find that extending the open future principle to delineate the scope of NIPT is theoretically flawed. However, they suggest that it can be used in counseling for prenatal screening to encourage parents' reflection on the implications of knowing for the sake of knowing on their future children and their relationship with them.
JOURNAL OF BIOETHICAL INQUIRY
(2023)
Article
Biochemistry & Molecular Biology
Ilse Parijs, Nathalie Brison, Leen Vancoillie, Machteld Baetens, Bettina Blaumeiser, Sebastien Boulanger, Julie Desir, Boyan Dimitrov, Nathalie Fieremans, Katrien Janssens, Sandra Janssens, Axel Marichal, Bjorn Menten, Colombine Meunier, Kim Van Berkel, Ann Van Den Bogaert, Koenraad Devriendt, Kris Van Den Bogaert, Joris Robert Vermeesch
Summary: Maternally inherited 15q11-q13 duplications are associated with more severe neurodevelopmental anomalies, while paternally inherited duplications are normal or associated with milder phenotypes. Our analysis of low coverage genome-wide cell-free DNA sequencing data from pregnant women confirms this difference in impact and recommends appropriate genetic counselling for women with 15q11-q13 duplications identified during non-invasive prenatal screening.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Maria Siermann, Ophelia Valcke, Joris Robert Vermeesch, Taneli Raivio, Olga Tsuiko, Pascal Borry
Summary: A qualitative study was conducted on healthcare professionals' perspectives towards PGT-P. Most professionals believed that it is premature to implement PGT-P due to ethical concerns and presented various considerations including validity, limitations, and potential benefits.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Jhih-Rong Lin, Yingjie Zhao, M. Reza Jabalameli, Nha Nguyen, Joydeep Mitra, Ann Swillen, Jacob A. S. Vorstman, Eva W. C. Chow, Marianne van den Bree, Beverly S. Emanuel, Joris R. Vermeesch, Michael J. Owen, Nigel M. Williams, Anne S. Bassett, Donna M. McDonald-McGinn, Raquel E. Gur, Carrie E. Bearden, Bernice E. Morrow, Herbert M. Lachman, Zhengdong D. Zhang
Summary: 22q11.2 deletion is a strong genetic risk factor for schizophrenia. Whole-genome sequencing of schizophrenia cases and controls with this deletion revealed the effects of rare coding variants in modifier genes, contributing to the pathogenesis of schizophrenia. The modifier genes affected synaptic function and developmental disorders and were coexpressed with 22q11.2 genes in specific brain regions.
MOLECULAR PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Maria Francesca Viola, Marta Chavero-Pieres, Elodie Modave, Marcello Delfini, Nathalie Stakenborg, Maria Cuende Estevez, Naomi Fabre, Iris Appeltans, Tobie Martens, Katy Vandereyken, Hannah Theobald, Jens Van Herck, Philippe Petry, Simon Verheijden, Sebastiaan De Schepper, Alejandro Sifrim, Zhaoyuan Liu, Florent Ginhoux, Mohamad Azhar, Andreas Schlitzer, Gianluca Matteoli, Katrin Kierdorf, Marco Prinz, Pieter Vanden Berghe, Thierry Voet, Guy Boeckxstaens
Summary: Development and maturation of the enteric nervous system (ENS) relies on the actions of resident macrophages, which prune synapses and phagocytose enteric neurons in early life. After weaning, these macrophages continue to interact closely with the ENS and acquire a neurosupportive phenotype. This interaction is mediated by transforming growth factor-beta produced by the ENS, and disruption of this communication leads to loss of enteric neurons and altered intestinal transit.
Review
Genetics & Heredity
Katy Vandereyken, Alejandro Sifrim, Bernard Thienpont, Thierry Voet
Summary: The joint analysis of multiple molecular modalities from single cells, such as the genome, epigenome, transcriptome, proteome, and metabolome, is transforming our understanding of cell biology in health and disease. This review discusses the advances in single-cell and spatial multi-omics technologies and the computational strategies for integrating information across these molecular layers. It also highlights their impact on fundamental cell biology and translational research, current challenges, and future prospects.
NATURE REVIEWS GENETICS
(2023)
Editorial Material
Genetics & Heredity
Lisa Hui, Katie Ellis, Dora Mayen, Mark D. D. Pertile, Rebecca Reimers, Luming Sun, Joris Vermeesch, Neeta L. L. Vora, Lyn S. S. Chitty, SPD Board of Directors
PRENATAL DIAGNOSIS
(2023)
Letter
Medical Laboratory Technology
Margot van Riel, Yan Zhao, Tatjana Jatsenko, Lore Lannoo, Dirk Timmerman, Joris R. Vermeesch
CLINICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Justine Lengrand, Ievgenia Pastushenko, Sebastiaan Vanuytven, Yura Song, David Venet, Rahul M. Sarate, Melanie Bellina, Virginie Moers, Alice Boinet, Alejandro Sifrim, Nicolas Rama, Benjamin Ducarouge, Jens Van Herck, Christine Dubois, Samuel Scozzaro, Sophie Lemaire, Sarah Gieskes, Sophie Bonni, Amandine Collin, Nicolas Braissand, Justine Allard, Egor Zindy, Christine Decaestecker, Christos Sotiriou, Isabelle Salmon, Patrick Mehlen, Thierry Voet, Agnes Bernet, Cedric Blanpain
Summary: Epithelial-to-mesenchymal transition (EMT) plays a crucial role in cancer initiation, progression, metastasis, and resistance to therapy. In this study, the upregulation of netrin-1 in skin squamous cell carcinoma (SCC) was found to induce EMT, and pharmacological inhibition of netrin-1 decreased EMT and enhanced chemotherapy sensitivity. These findings suggest a potential therapeutic strategy for targeting EMT in cancer.
Article
Biochemistry & Molecular Biology
Marie De Borre, Huiwen Che, Qian Yu, Lore Lannoo, Kobe De Ridder, Leen Vancoillie, Pauline Dreesen, Mika Van Den Ackerveken, Mio Aerden, Eva Galle, Jeroen Breckpot, Joachim Van Keirsbilck, Wilfried Gyselaers, Koen Devriendt, Joris Robert Vermeesch, Kristel Van Calsteren, Bernard Thienpont
Summary: By profiling the cell-free DNA methylation of plasma, it is possible to identify the risk of preeclampsia in early pregnancy, providing guidance for prevention and treatment.
Article
Genetics & Heredity
Lore Lannoo, Joke Van Camp, Nathalie Brison, Ilse Parijs, Leen Vancoillie, Kris van den Bogaert, Joris Robert Vermeesch, Koen Devriendt, Kristel Van Calsteren
Summary: This study assessed the maternal characteristics and comorbidities in patients with persistent uninterpretable non-invasive prenatal testing (NIPT) and evaluated the association with adverse pregnancy outcomes. The findings showed that patients with persistent uninterpretable NIPT were more likely to have obesity, multiple pregnancies, and obstetric complications, and had a higher incidence of adverse pregnancy outcomes compared to the general population.
PRENATAL DIAGNOSIS
(2023)
Article
Genetics & Heredity
Yingjie Zhao, Yujue Wang, Lijie Shi, Donna M. McDonald-McGinn, T. Blaine Crowley, Daniel E. McGinn, Oanh T. Tran, Daniella Miller, Jhih-Rong Lin, Elaine Zackai, H. Richard Johnston, Eva W. C. Chow, Jacob A. S. Vorstman, Claudia Vingerhoets, Therese van Amelsvoort, Doron Gothelf, Ann Swillen, Jeroen Breckpot, Joris R. Vermeesch, Stephan Eliez, Maude Schneider, Marianne B. M. van den Bree, Michael J. Owen, Wendy R. Kates, Gabriela M. Repetto, Vandana Shashi, Kelly Schoch, Carrie E. Bearden, M. Cristina Digilio, Marta Unolt, Carolina Putotto, Bruno Marino, Maria Pontillo, Marco Armando, Stefano Vicari, Kathleen Angkustsiri, Linda Campbell, Tiffany Busa, Damian Heine-Suner, Kieran C. Murphy, Declan Murphy, Sixto Garcia-Minaur, Luis Fernandez, Zhengdong D. Zhang, Elizabeth Goldmuntz, Raquel E. Gur, Beverly S. Emanuel, Deyou Zheng, Christian R. Marshall, Anne S. Bassett, Tao Wang, Bernice E. Morrow
Summary: Congenital heart disease (CHD) in patients with 22q11.2 deletion syndrome (22q11.2DS) may be influenced by genetic modifiers in the TBX1 gene network. Chromatin regulatory genes including EP400, KAT6A, KMT2C, KMT2D, NSD1, CHD7, and PHF21A are identified as potential modifiers. These findings suggest shared mechanisms involving the TBX1 gene network in the etiology of CHD.
NPJ GENOMIC MEDICINE
(2023)
Meeting Abstract
Oncology
Haixi Yan, Jonas Demeulemeester, Annelien Verfaillie, Cristina Cotobal Martin, Tom Kaufmann, Roland Schwarz, Thierry Voet, Simone Zaccaria, Adrienne Flanagan, Maxime Tarabichi, Peter Van Loo
