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
Oncology
Fumi Murakami, Yumi Tsuboi, Yuka Takahashi, Yoshiya Horimoto, Kaoru Mogushi, Takeshi Ito, Mitsuru Emi, Daisuke Matsubara, Tatsuhiro Shibata, Mitsue Saito, Yoshinori Murakami
Summary: Copy number variation (CNV) is a common polymorphism in the human genome, with somatic alterations at CNV sites detected in 39.9% of the CNV probes examined in invasive breast cancers. The most frequently altered regions included gains of 1q21-22, 8q21-24, 1q44, 3q11, and losses of 16q22-24. Gene ontology analysis revealed correlations between CNAs and transcription/RNA metabolism in relation to HER2 positivity and menopausal status in breast cancer patients.
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)
Article
Psychiatry
Hojka Gregoric Kumperscak, Danijela Krgovic, Maja Drobnic Radobuljac, Nina Senica, Andreja Zagorac, Nadja Kokalj Vokac
Summary: This study analyzed CNVs in patients with EOS and EOB, identifying genetic variations associated with schizophrenia and/or bipolar disorder. Findings included CNVs involving the PAK2, ARHGAP11B, and PRODH genes, as well as unique chromosome abnormalities such as the 47, XYY karyotype in EOB patients.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Obstetrics & Gynecology
Mina Popovic, Lorena Borot, Aline R. Lorenzon, Ana Luiza Rossi de Castro Lopes, Denny Sakkas, Belen Lledo, Ruth Morales, Jose Antonio Ortiz, Nikolaos P. Polyzos, Monica Parriego, Felicitas Azpiroz, Micaela Galain, Aida Pujol, Bjorn Menten, Lien Dhaenens, Frauke Vanden Meerschaut, Dominic Stoop, Maria Rodriguez, Enrique Perez de la Blanca, Amelia Rodriguez, Rita Vassena
Summary: The diagnosis of mosaicism affects the ploidy rates across different providers offering preimplantation genetic testing for aneuploidies (PGT-A), with providers reporting low rates of mosaicism having significantly higher euploidy rates.
HUMAN REPRODUCTION
(2023)
Article
Agronomy
Madhab Kumar Sen, Katerina Hamouzova, Jakub Mikulka, Rohit Bharati, Pavlina Kosnarova, Pavel Hamouz, Amit Roy, Josef Soukup
Summary: The study identified mechanisms of resistance to ALS-inhibiting herbicides in a Bromus sterilis biotype, including reduced sensitivity to pyroxsulam, cross-resistance to other herbicides, and possible overexpression of target genes and enhanced metabolism by cytochrome P450s. These findings emphasize the need for monitoring herbicide resistance in brome populations in Europe and the use of alternate herbicides in integrated weed management to delay the evolution of resistance.
PEST MANAGEMENT SCIENCE
(2021)
Article
Gastroenterology & Hepatology
Mariola Monika Golas, Bastian Gunawan, Meliha Cakir, Silke Cameron, Christina Enders, Torsten Liersch, Laszlo Fuezesi, Bjoern Sander
Summary: Colorectal carcinomas progress through heterogeneous pathways, with different genetic events observed in tumors located at different sites and with varying levels of chromosomal imbalance. The timing of specific genetic events in CRC may influence its metastatic potential, with distinct genetic pathways observed in cases with lymph node or distant metastasis. The 'Vogelgram' concept, focusing on the accumulation of genetic changes, is supported in CRCs characterized by chromosomal instability.
COLORECTAL DISEASE
(2022)
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
Neurosciences
Timothy E. Richardson, Jamie M. Walker, Kalil G. Abdullah, Samuel K. McBrayer, Mariano S. Viapiano, Zarmeen M. Mussa, Nadejda M. Tsankova, Matija Snuderl, Kimmo J. Hatanpaa
Summary: Chromosomal instability (CIN) is a fundamental property of cancer and a key mechanism of tumorigenesis and progression. It is found in various cancers and is associated with poor clinical outcomes. However, there have been relatively few studies on this process, mainly due to the difficulty of measuring it clinically.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Vishal H. Oza, Jennifer L. Fisher, Roshan Darji, Brittany N. Lasseigne
Summary: Genomic instability is an important feature in cancer and other diseases. Measuring chromosomal alterations can characterize clinical and biological phenotypes associated with these diseases. However, there is a lack of a single tool to calculate and compare the various chromosomal instability scores. In this study, an R package called CINmetrics is provided, which calculates six different chromosomal instability scores and allows for direct comparison between them. It is demonstrated how these scores differ by applying CINmetrics to breast cancer data from The Cancer Genome Atlas (TCGA). The package can be accessed at https:/cran.rproject.org/package=CINmetrics and https://github.com/ lasseignelab/CINmetrics.
Review
Oncology
Yu-Yang Liao, Wen-Ming Cao
Summary: Chromosomal instability (CIN) is an important marker of cancer, closely related to tumorigenesis, disease progression, treatment efficacy, and patient prognosis. Its clinical significance remains unclear due to limitations in current detection methods. However, studies have shown that CIN is present in 89% of invasive breast cancer cases, indicating its potential for breast cancer diagnosis and treatment. This review provides insights into the types of CIN, detection methods, and its impact on breast cancer development, treatment, and prognosis, aiming to serve as a reference for researchers and clinicians.
FRONTIERS IN ONCOLOGY
(2023)
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
Stacey J. Scott, Xiaodun Li, Sriganesh Jammula, Ginny Devonshire, Catherine Lindon, Rebecca C. Fitzgerald, Pier Paolo D'Avino
Summary: Polyloidy plays a significant role in promoting chromosomal instability, genome evolution, and heterogeneity in cancer cells. The study on esophageal adenocarcinoma (EAC) revealed that the likely origin of polyploidy is due to mitotic failure caused by problems in chromosomal attachments, shedding light on cancer evolution and diversification for potential classification and treatment improvements.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Genetics & Heredity
Smruthy Sivakumar, F. Anthony San Lucas, Yasminka A. Jakubek, Zuhal Ozcan, Jerry Fowler, Paul Scheet
Summary: This study improves the sensitivity in identifying SCNAs by modeling B allele frequencies jointly and provides AI summaries for various tumor sites in TCGA. The research shows a high proportion of AI events and reveals recurrent events as well as previously uncharacterized patterns of cnLOH.
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
Oncology
Kavya Prasad, Mathew Bloomfield, Hagai Levi, Kristina Keuper, Sara Bernhard, Nicolaas C. Baudoin, Gil Leor, Yonatan Eliezer, Maybelline Giam, Cheng Kit Wong, Giulia Rancati, Zuzana Storchova, Daniela Cimini, Uri Ben-David
Summary: The interactions between whole-genome duplication and aneuploidy are crucial for tumor evolution, emphasizing the importance of considering genome status in the analysis and modeling of cancer aneuploidy.
Article
Biology
Federica Scotto di Carlo, Sharon Russo, Francesc Muyas, Maria Mangini, Lorenza Garribba, Laura Pazzaglia, Rita Genesio, Flavia Biamonte, Anna Chiara De Luca, Stefano Santaguida, Katia Scotlandi, Isidro Cortes-Ciriano, Fernando Gianfrancesco
Summary: Profilin 1, encoded by PFN1, is a protein that plays a tumor suppressive role in various adenocarcinomas and pagetic osteosarcomas. However, its exact contribution to tumor development is not fully understood. This study shows that inactivation of Profilin 1 leads to multiple mitotic defects, resulting in chromosomal instability and genome rearrangements in pagetic osteosarcomas. Mechanistically, Profilin 1 is involved in regulating cell division and its deficiency impairs actin filament supply during cytokinesis.
COMMUNICATIONS BIOLOGY
(2023)
Article
Oncology
Patricia Altea-Manzano, Ginevra Doglioni, Yawen Liu, Alejandro M. Cuadros, Emma Nolan, Juan Fernandez-Garcia, Qi Wu, Melanie Planque, Kathrin Julia Laue, Florencia Cidre-Aranaz, Xiao-Zheng Liu, Oskar Marin-Bejar, Joke Van Elsen, Ines Vermeire, Dorien Broekaert, Sofie Demeyer, Xander Spotbeen, Jakub Idkowiak, Aurelie Montagne, Margherita Demicco, H. Furkan Alkan, Nick Rabas, Carla Riera-Domingo, Francois Richard, Tatjana Geukens, Maxim De Schepper, Sophia Leduc, Sigrid Hatse, Yentl Lambrechts, Emily Jane Kay, Sergio Lilla, Alisa Alekseenko, Vincent Geldhof, Bram Boeckx, Celia de la Calle Arregui, Giuseppe Floris, Johannes V. Swinnen, Jean-Christophe Marine, Diether Lambrechts, Vicent Pelechano, Massimiliano Mazzone, Sara Zanivan, Jan Cools, Hans Wildiers, Veronique Baud, Thomas G. P. Gruenewald, Uri Ben-David, Christine Desmedt, Ilaria Malanchi, Sarah-Maria Fendt
Summary: The formation of pre-metastatic niche and high-fat diet can increase palmitate availability in future organs of metastases, promoting NF-kappa B acetylation and inducing metastatic signaling. Deletion of acetyltransferase and palmitoyltransferase reduces metastasis formation.
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
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
Oncology
Tian-Gen Chang, Yingying Cao, Eldad D. Shulman, Uri Ben-David, Alejandro A. Schaffer, Eytan Ruppin
Summary: This study examined the ability of two common copy-number alteration (CNA) scores, AS and FGA, to predict survival following immunotherapy in 3139 patients with different cancer types. The results showed that AS and FGA could predict overall survival in both high-TMB and low-TMB patients, but their predictive power was limited to only a few specific cancer types. Larger sample sizes are needed to determine their clinical utility in other cancer types. Additionally, a simple elbow-point-based method was proposed to determine the cutoff for calling CNAs.
NPJ PRECISION ONCOLOGY
(2023)
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)
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)
