Article
Biochemistry & Molecular Biology
Francesco Reggiani, Marianna Ambrosio, Michela Croce, Enrica Teresa Tanda, Francesco Spagnolo, Edoardo Raposio, Mariangela Petito, Zeinab El Rashed, Alessandra Forlani, Ulrich Pfeffer, Adriana Agnese Amaro
Summary: The metastatic risk of uveal melanoma (UM) is determined by limited molecular lesions, somatic mutations, and copy number alterations. BAP1 mutations are always associated with M3 in high-risk patients, while other features such as 6p, 8q, M3, and SF3B1 mutation are present independently. Chr8q gain is frequently associated with chr3 disomy. Gene expression data analysis reveals two clusters, one enriched in metastatic samples with 8q|M3, BAP1|M3, and the other mainly containing low-risk samples with 6p combined with either 8q or SF3B1. Some gene expression events become significant when considering combinations of risk features, indicating additive action. The independence of risk factors supports a random risk model of UM metastasis without an obligatory sequence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Satoshi Kaito, Atsushi Iwama
Summary: Polycomb repressive complexes play a crucial role in maintaining hematopoietic stem cells and mutations in corresponding genes are associated with hematologic malignancies, leading to resistance to chemotherapy and poor prognosis. Recent studies have revealed that these gene mutations are druggable targets, and inhibitors have shown therapeutic efficacy for tumors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Min Gao, Yongwen Li, Peijun Cao, Hongyu Liu, Jun Chen, Shirong Kang
Summary: This paper reviews the importance of PRC2 in the development and progression of lung cancer, and explores its role in tumor immunity, cellular behavior regulation, and drug treatment.
FRONTIERS IN ONCOLOGY
(2023)
Article
Cell Biology
Ludivine Raby, Pamela Volkel, Shaghayegh Hasanpour, Julien Cicero, Robert-Alain Toillon, Eric Adriaenssens, Isabelle Van Seuningen, Xuefen Le Bourhis, Pierre-Olivier Angrand
Summary: This study reports on a zebrafish line with a null allele of eed, a key component of PRC2, and reveals severe defects in digestive organs and brain neuronal differentiation in homozygous eed-deficient mutants, leading to death. Additionally, loss of PRC2 function in zebrafish increases larval activity and highlights its potential as a model for studying human pathologies linked to PRC2 dysfunction and reduced H3K27me3 levels.
Review
Genetics & Heredity
Pooja Flora, Gil Dalal, Idan Cohen, Elena Ezhkova
Summary: Resident stem cells in adult tissues play a crucial role in maintaining, repairing, and regenerating tissues throughout organisms' lifetimes. The process of stem cell renewal and differentiation is tightly regulated, with epigenetic regulators such as polycomb group proteins playing a key role in maintaining homeostasis and regenerative balance in adult tissues.
Article
Plant Sciences
Tianqing Zhu, Jiwen Hu, Xiaowei Yang, Lisheng Kong, Juanjuan Ling, Junhui Wang, Sanping An
Summary: This study characterizes the PRC2 core component genes in the conifer species P. abies, revealing their involvement in cell reprogramming during seed and embryo development. These findings may contribute to a better understanding of embryonic potential and development in conifers.
Article
Oncology
Maksim Erokhin, Olga Chetverina, Balazs Gyorffy, Victor V. Tatarskiy, Vladic Mogila, Alexander A. Shtil, Igor B. Roninson, Jerome Moreaux, Pavel Georgiev, Giacomo Cavalli, Darya Chetverina
Summary: PRC2 is a complex involved in transcriptional repression through histone methylation, with dysregulation linked to tumor development. This study analyzed clinical correlations of PRC2 subunit genes in tumor samples, identifying cancer types responsive to PRC2 inhibition and potential sensitivity markers for PRC2-targeting drugs.
Article
Cell Biology
Zi-Mu Zhang, Hai-Bo Cao, Zhi-Heng Li, Ran Zhuo, Yan-Fang Tao, Xiao-Lu Li, Gen Li, Xin-Mei Liao, Fang Fang, Yi Xie, Di Wu, Hai-Rong Wang, Jian-Wei Wang, Yan-Ling Chen, Juan-Juan Yu, Si-Qi Jia, Ran-Dong Yang, Xin-Yi Guo, Yang Yang, Chen-Xi Feng, Yun-Yun Xu, Guang-Hui Qian, Jian Pan
Summary: Recent studies have highlighted the crucial role of SAPCD2 in promoting neuroblastoma (NB) progression by directly binding to cytoplasmic E2F7 and impacting gene expression related to cell cycle and chromosome instability. Additionally, the study revealed a potential therapeutic approach for NB by targeting SAPCD2 and manipulating the E2F signaling pathway.
CELL DEATH & DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Ahmed Malki, Rasha Abu ElRuz, Ishita Gupta, Asma Allouch, Semir Vranic, Ala-Eddin Al Moustafa
Summary: Colorectal cancer is the second leading cause of cancer-related mortality rates worldwide, with its prevalence still on the rise. Dysregulation of several cellular signaling pathways in CRC leads to malignant phenotypes. Studying signaling pathways helps elucidate the mechanisms of CRC progression and pharmacotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Joanna Patrycja Wroblewska, Michal Stefan Lach, Marcin Rucinski, Igor Piotrowski, Lukasz Galus, Wiktoria Maria Suchorska, Stephanie Kreis, Andrzej Marszalek
Summary: The study found that miRNAs extracted from exosomes of UM patients could be potential biomarkers for diagnosis and metastatic spread of UM.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Agronomy
Zhongling WU, Jiehua QIU, Huanbin SHI, Chuyu LIN, Jiangnan YUE, Zhiquan LIU, Wei XIE, Naweed I. N. Aqvi, Yanjun KOU, Zeng TAO
Summary: This study reveals the essential role of the core subunits of PRC2 in the pathogenicity of Magnaporthe oryzae to rice. These subunits are required for the establishment of H3K27me3 modification, which is involved in the transcriptional regulation of numerous genes. Interestingly, the de-repression of genes associated with H3K27me3 modification is closely related to effector-mediated host immunity and host environment adaption.
Article
Multidisciplinary Sciences
Ogul E. Uner, Thonnie Rose O. See, Eszter Szalai, Hans E. Grossniklaus, Gustav Stalhammar
Summary: The study found that BAP1 mutations in uveal melanoma occur early in tumor growth, typically appearing in the initial stages, and coincide with the seeding of micrometastases.
SCIENTIFIC REPORTS
(2021)
Article
Plant Sciences
Adji Baskoro Dwi Nugroho, Sujeong Kim, Sang Woo Lee, Dong-Hwan Kim
Summary: Polycomb group proteins (PcG) are important for developmental programs in plants. CLF, a PcG component in Arabidopsis, has a homolog in Brassica rapa ssp. trilocularis, called BrCLF. BrCLF participates in developmental processes, stress signaling, and stress-responsive metabolism in B. rapa. This study contributes to understanding the molecular mechanism of PcG-mediated regulation in development and stress responses in B. rapa.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Sandra Garcia-Mulero, Maria Henar Alonso, Luis P. del Carpio, Rebeca Sanz-Pamplona, Josep M. Piulats
Summary: Uveal melanoma (UM) is a common malignant eye tumor with poor prognosis, characterized by a unique immunosuppressive microenvironment. Our study found that high immune and stromal scores in the UM microenvironment were associated with poor prognosis, while lymphocytic infiltration was related to poor prognosis and only B cells were associated with a more favorable prognosis. Samples with high angiogenic and inflammatory phenotypes exhibited poor prognosis and metabolic activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Michael S. Parappilly, Yuki Chin, Riley M. Whalen, Ashley N. Anderson, Trinity S. Robinson, Luke Strgar, Thomas L. Sutton, Patrick Conley, Christopher Klocke, Summer L. Gibbs, Young Hwan Chang, Guanming Wu, Melissa H. Wong, Alison H. Skalet
Summary: This study discovered a new population of tumor cells, called circulating hybrid cells, in the blood of uveal melanoma patients. The number of circulating hybrid cells at the time of initial treatment predicts the future development of disease spread. These cells have the potential to be used as a non-invasive and repeatable liquid biopsy for uveal melanoma patients.
Review
Pathology
Sihan Wu, Vineet Bafna, Howard Y. Chang, Paul S. Mischel
Summary: This review discusses the formation and function of circular, extrachromosomal pieces of DNA (ecDNA) found in cancer, as well as their contribution to tumor pathogenesis, drug resistance, and accelerated cancer evolution.
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE
(2022)
Article
Multidisciplinary Sciences
Erik N. Bergstrom, Jens Luebeck, Mia Petljak, Azhar Khandekar, Mark Barnes, Tongwu Zhang, Christopher D. Steele, Nischalan Pillay, Maria Teresa Landi, Vineet Bafna, Paul S. Mischel, Reuben S. Harris, Ludmil B. Alexandrov
Summary: This study provides a comprehensive characterization of clustered mutations and small insertions and deletions in cancer genomes. The results show that clustered mutations are enriched in driver genes and associated with differential gene expression and overall survival. Different mutational processes contribute to clustered insertions and deletions, including specific signatures in tobacco smokers and homologous-recombination-deficient cancers. APOBEC3 plays a significant role in clustered substitutions, although only a small percentage matches APOBEC3 patterns. The study also reveals the associations between the activation-induced deaminase (AID) and APOBEC3 family of deaminases with kataegis (longer strand-coordinated events).
Article
Chemistry, Multidisciplinary
Merav Antman-Passig, Eitan Wong, Georgia R. Frost, Christian Cupo, Janki Shah, Albert Agustinus, Ziyu Chen, Chiara Mancinelli, Maikel Kamel, Thomas Li, Lauren A. Jonas, Yue-Ming Li, Daniel A. Heller
Summary: The researchers developed a near-infrared optical nanosensor that can detect the presence of A beta in live cells and mice. The sensor selectively responds to A beta through solvatochromic modulation, allowing for tracking of A beta accumulation. This technology provides insight into the molecular mechanisms underlying A beta neurotoxicity in the development of Alzheimer's disease.
Review
Genetics & Heredity
Vineet Bafna, Paul S. Mischel
Summary: In cancer, the amplification of oncogenes on circular extrachromosomal DNA (ecDNA) elements drives tumor formation and progression. ecDNA increases oncogene copy number, promotes genetic heterogeneity, and results in treatment resistance. It also alters the transcriptional landscape of tumors. Current tools are limited in resolving the complex changes in DNA structure and dynamics caused by ecDNA, but new tools are emerging.
ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS
(2022)
Review
Biochemistry & Molecular Biology
King L. Hung, Paul S. Mischel, Howard Y. Chang
Summary: Amplification of oncogene expression through extrachromosomal DNA is prevalent in human cancer and is associated with poor outcomes. The formation of ecDNA hubs enables profound changes in gene regulation and allows for potent and combinatorial gene activation. Technological advancements in studying ecDNA gene regulation and structure provide insights into the distinct rules that govern cancer genes beyond chromosomes.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Genetics & Heredity
Joshua T. Lange, John C. Rose, Celine Y. Chen, Yuriy Pichugin, Liangqi Xie, Jun Tang, King L. Hung, Kathryn E. Yost, Quanming Shi, Marcella L. Erb, Utkrisht Rajkumar, Sihan Wu, Sabine Taschner-Mandl, Marie Bernkopf, Charles Swanton, Zhe Liu, Weini Huang, Howard Y. Chang, Vineet Bafna, Anton G. Henssen, Benjamin Werner, Paul S. Mischel
Summary: Random segregation of extrachromosomal DNA contributes to intratumoral heterogeneity and facilitates the rapid adaptation of human tumor cells to anticancer drugs. Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumor growth, drug resistance and shorter survival. Through theoretical models, unbiased image analysis, CRISPR-based ecDNA tagging with live-cell imaging and CRISPR-C, it is shown that random ecDNA inheritance results in extensive intratumoral ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted treatment.
Article
Genetics & Heredity
King L. Hung, Jens Luebeck, Siavash R. Dehkordi, Caterina Colon, Rui Li, Ivy Tsz-Lo Wong, Ceyda Coruh, Prashanthi Dharanipragada, Shirley H. Lomeli, Natasha E. Weiser, Gatien Moriceau, Xiao Zhang, Chris Bailey, Kathleen E. Houlahan, Wenting Yang, Rocio Chamorro Gonzalez, Charles Swanton, Christina Curtis, Mariam Jamal-Hanjani, Anton G. Henssen, Julie A. Law, William J. Greenleaf, Roger S. Lo, Paul S. Mischel, Vineet Bafna, Howard Y. Chang
Summary: The study demonstrates the isolation of extrachromosomal DNA (ecDNA) containing oncogenes from human cancer cells using CRISPR-CATCH technology, followed by methylation profiling and identification of unique features compared to chromosomal loci.
Article
Multidisciplinary Sciences
Zhongchi Li, Vivien Low, Valbona Luga, Janet Sun, Ethan Earlie, Bobak Parang, Kripa Shobana Ganesh, Sungyun Cho, Jennifer Endress, Tanya Schild, Mengying Hu, David Lyden, Wenbing Jin, Chunjun Guo, Noah Dephoure, Lewis C. Cantley, Ashley M. Laughney, John Blenis
Summary: Systemic metabolic shifts during aging and local metabolic alterations of a tumor cooperate to establish a unique tumor microenvironment (TME). Methylmalonic acid (MMA) activates fibroblasts in the TME, which release IL-6 loaded extracellular vesicles (EVs) that drive cancer progression.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Thomas J. West, Junfeng Bi, Francisco Martinez-Pena, Ellis J. Curtis, Nathalia R. . Gazaniga, Paul S. Mischel, Luke L. Lairson
Summary: In this study, a prodrug form of YM155 called aYM155 was designed, synthesized, and characterized. aYM155 displayed potent cell killing activity against GBM and EGFRvIII-expressing cells, and was activated in a cell-type-dependent manner. It was also found that YM155 interacted with receptor-interacting protein kinase 2 (RIPK2) and exhibited survivin-suppressing and apoptosis-inducing activities. In an orthotopic intracranial GBM xenograft model, aYM155 significantly inhibited brain tumor growth and showed cell-type selective survivin-based pharmacodynamic effects.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Albert S. S. Agustinus, Duaa Al-Rawi, Bhargavi Dameracharla, Ramya Raviram, Bailey S. C. L. Jones, Stephanie Stransky, Lorenzo Scipioni, Jens Luebeck, Melody Di Bona, Danguole Norkunaite, Robert M. M. Myers, Mercedes Duran, Seongmin Choi, Britta Weigelt, Shira Yomtoubian, Andrew McPherson, Eleonore Toufektchan, Kristina Keuper, Paul S. S. Mischel, Vivek Mittal, Sohrab P. P. Shah, John Maciejowski, Zuzana Storchova, Enrico Gratton, Peter Ly, Dan Landau, Mathieu F. F. Bakhoum, Richard P. P. Koche, Simone Sidoli, Vineet Bafna, Yael David, Samuel F. F. Bakhoum
Summary: This study shows that chromosomal instability and epigenetic alterations are mechanically linked in advanced and metastatic cancers. Misalignment of mitotic chromosomes and rupture of the micronuclear envelope disrupt normal histone post-translational modifications. Micronuclei exhibit differences in chromatin accessibility, leading to epigenetic dysregulation and heritable abnormalities in chromosome accessibility. Chromosomal instability not only alters genomic copy number but also promotes epigenetic reprogramming and heterogeneity in cancer.
Article
Multidisciplinary Sciences
Ramya Raviram, Anugraha Raman, Sebastian Preissl, Jiangfang Ning, Shaoping Wu, Tomoyuki Koga, Kai Zhang, Cameron W. Brennan, Chenxu Zhu, Jens Luebeck, Kinsey Van Deynze, Jee Yun Han, Xiaomeng Hou, Zhen Ye, Anna K. Mischel, Yang Eric Li, Rongxin Fang, Tomas Baback, Joshua Mugford, Claudia Z. Han, Christopher K. Glass, Cathy L. Barr, Paul S. Mischel, Vineet Bafna, Laure Escoubet, Bing Ren, Clark C. Chen
Summary: In 2021, glioblastoma, the most common form of adult brain cancer, was reclassified by the World Health Organization into two subtypes based on genetic characteristics. The study analyzed the chromatin accessibility and transcription profiles of clinical samples from both types of tumors, revealing intratumoral heterogeneity and shared chromatin structure among tumor cells. Silencing specific transcription factors suppressed tumor growth, suggesting a potential therapeutic target for addressing the challenges associated with intratumoral heterogeneity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Meeting Abstract
Oncology
Paul S. Mischel
Meeting Abstract
Oncology
Albert S. Agustinus, Ramya Raviram, Bhargavi Dameracharla, Jens Luebeck, Stephanie Stransky, Lorenzo Scipioni, Robert M. Myers, Melody Di Bona, Mercedes Duran, Britta Weigelt, Shira Yomtoubian, Eleonore Toufektchan, Paul S. Mischel, Vivek Mittal, Sohrab Shah, John Maciejowski, Enrico Gratton, Peter Ly, Mathieu F. Bakhoum, Dan Landau, Vineet Bafna, Simone Sidoli, Yael David, Samuel F. Bakhoum