Article
Oncology
Martina K. Zowada, Stephan M. Tirier, Sebastian M. Dieter, Teresa G. Krieger, Ava Oberlack, Robert Lorenz Chua, Mario Huerta, Foo Wei Ten, Karin Laaber, Jeongbin Park, Katharina Jechow, Torsten Mueller, Mathias Kalxdorf, Mark Kriegsmann, Katharina Kriegsmann, Friederike Herbst, Jeroen Krijgsveld, Martin Schneider, Roland Eils, Hanno Glimm, Christian Conrad, Claudia R. Ball
Summary: Different cell types with tumor-initiating cell (TIC) activity in colorectal cancer (CRC) show distinct gene expression patterns at single-cell level. Metabolic states are closely linked to TIC activity in primary CRC cultures, suggesting oxidative phosphorylation as a potential target for novel therapies. Transcriptional heterogeneity at single-cell resolution identifies functional states during TIC differentiation and may reveal novel vulnerabilities in human CRC.
Article
Multidisciplinary Sciences
C. Megan Young, Laurent Beziaud, Pierre Dessen, Angela Madurga Alonso, Albert Santamaria-Martinez, Joerg Huelsken
Summary: This study examines the metabolic adaptations of metastasis-initiating cells (MICs) in female breast cancer and how those shape their metastatic phenotype. The findings demonstrate that MICs specifically alter their metabolism to efficiently colonize distant organs, and understanding these mechanisms may help control cancer progression.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Jae-Il Choi, Sung Ill Jang, Jaehyun Hong, Chul Hoon Kim, Soon Sung Kwon, Joon Seong Park, Jong-Baeck Lim
Summary: In this study, it was demonstrated that CD44(+), CD24(+) and EpCAM(+) cancer-initiating cells (CICs) were enriched in patient-derived organoids of PDAC. CD44-expressing CICs formed lumen structures within the organoids. Additionally, CD44(-) cancer cells from the organoids could re-form organoids and be re-programed as CD44-expressing CICs. The study also showed that the maintenance of CICs in PDAC organoids was mediated by interactions with endothelial cells through Wnt and Notch signaling pathways.
Article
Biochemistry & Molecular Biology
Masaya Yamazaki, Shinjiro Hino, Shingo Usuki, Yoshihiro Miyazaki, Tatsuya Oda, Mitsuyoshi Nakao, Takaaki Ito, Kazuya Yamagata
Summary: Tumor-initiating cells with high expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) have partial epithelial-mesenchymal transition (EMT)-like signature and act as the origin of heterogeneous tumor cells in PDAC. ROR1 depletion suppresses tumor growth, recurrence after chemotherapy, and metastasis by inducing the expression of Aurora kinase B (AURKB) through activating E2F via c-Myc. ROR1 is transcriptionally dependent on YAP/BRD4 binding at the enhancer region and targeting this pathway reduces ROR1 expression and prevents PDAC growth.
Review
Cell Biology
Jiexi Li, Xingdi Ma, Deepavali Chakravarti, Shabnam Shalapour, Ronald A. DePinho
Summary: Colorectal cancer ranks as the third most common cancer in women, the fourth most common in men, and the fourth leading cause of cancer death globally. Incidence and mortality rates vary by race and ethnicity, with non-Hispanic blacks having the highest rates. In recent years, there has been a decline in the incidence of colorectal cancer in individuals over 50 years old.
GENES & DEVELOPMENT
(2021)
Article
Oncology
Brittney S. Harrington, Rahul Kamdar, Franklin Ning, Soumya Korrapati, Michael W. Caminear, Lidia F. Hernandez, Donna Butcher, Elijah F. Edmondson, Nadia Traficante, Joy Hendley, Madeline Australian Ovarian Canc Study, Madeline Gough, Rebecca Rogers, Rohan Lourie, Jyoti Shetty, Bao Tran, Fathi Elloumi, Abdalla Abdelmaksoud, Madhu Lal Nag, Krystyna Mazan-Mamczarz, Carrie D. House, John D. Hooper, Christina M. Annunziata
Summary: The study found that UGDH plays distinct roles in different molecular subtypes of epithelial ovarian cancer, influencing the tumor microenvironmental composition. UGDH is a strong potential therapeutic target in TICs, particularly in patients with the mesenchymal molecular subtype of EOC.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Review
Oncology
Romina Judith Walter, Steffen Joachim Sonnentag, Veronique Orian-Rousseau, Leonel Munoz-Sagredo
Summary: The cancer stem cell hypothesis suggests that tumors originate from a small population of cells with self-renewal capabilities, with differentiated cells potentially having tumor-suppressive effects. Understanding cell hierarchies and plasticity is crucial for investigating the interplay between cancer stem cells and differentiated cells.
Article
Oncology
Mikella Robinson, Samuel F. Gilbert, Jennifer A. Waters, Omar Lujano-Olazaba, Jacqueline Lara, Logan J. Alexander, Samuel E. Green, Gregory A. Burkeen, Omid Patrus, Zinia Sarwar, Ryne Holmberg, Christine Wang, Carrie D. House
Summary: The findings suggest that SOX2 may be a more consistent indicator of ovarian tumor initiating cells (TICs) that contribute to tumor repopulation following chemotherapy. Further studies evaluating SOX2 in TIC biology will enhance understanding of mechanisms driving ovarian cancer relapse.
Review
Immunology
Bouchra Ghazi, Adil El Ghanmi, Sarah Kandoussi, Amina Ghouzlani, Abdallah Badou
Summary: CAR T-cell therapy is a promising genetically engineered cell-based immunotherapy for cancer, but its application in solid tumors, including colorectal cancer, is still in the early stages. Major limitations of this therapy include high toxicity, relapses, and an impermeable tumor microenvironment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Nanoscience & Nanotechnology
Priya Dharmalingam, Krishnan Venkatakrishnan, Bo Tan
Summary: This study developed a multimode nanoplatform to investigate epigenetic changes in tumor-initiating cancer stem cells and explore their transformation signals following drug therapy. By utilizing surface-enhanced Raman scattering technology and dopant functionalization, biomarkers in tiCSCs can be analyzed label-free at the cellular level.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Shujiro Okuda, Yoshifumi Shimada, Yosuke Tajima, Kizuki Yuza, Yuki Hirose, Hiroshi Ichikawa, Masayuki Nagahashi, Jun Sakata, Yiwei Ling, Nobuaki Miura, Mika Sugai, Yu Watanabe, Shiho Takeuchi, Toshifumi Wakai
Summary: In colorectal cancer patients, distinct enriched bacteria were found in tumor and non-tumor tissues, with some bacteria associated with mutated genes and pathways. Campylobacter abundance was linked to failure of double-strand DNA break repairs, suggesting a potential role of bacterial infection in causing DNA damage in CRC development.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Oncology
Michael W. Caminear, Brittney S. Harrington, Rahul D. Kamdar, Michael J. Kruhlak, Christina M. Annunziata
Summary: The study found that disulfiram was more effective in reducing the viability of TICs compared to NCTs, affecting NF kappa B signaling, and was more suitable as a therapeutic to prevent EOC relapse.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Irawan Yusuf, Bens Pardamean, James W. Baurley, Arif Budiarto, Upik A. Miskad, Ronald E. Lusikooy, Arham Arsyad, Akram Irwan, George Mathew, Ivet Suriapranata, Rinaldy Kusuma, Muhamad F. Kacamarga, Tjeng W. Cenggoro, Christopher McMahan, Chase Joyner, Carissa Pardamean
Summary: The study conducted a genome-wide association study on colorectal cancer in Indonesians, identifying SNP associated with colorectal cancer risk and establishing a polygenic risk model. The findings help characterize the relationship between genetic variants and colorectal cancer risk in diverse Indonesian populations.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Shiki Fujino, Norikatsu Miyoshi, Aya Ito, Rie Hayashi, Masayoshi Yasui, Chu Matsuda, Masayuki Ohue, Masafumi Horie, Shinichi Yachida, Jun Koseki, Teppei Shimamura, Tsuyoshi Hata, Takayuki Ogino, Hidekazu Takahashi, Mamoru Uemura, Tsunekazu Mizushima, Yuichiro Doki, Hidetoshi Eguchi
Summary: High expression of POU5F1 is associated with colorectal cancer recurrence and liver metastasis. POU5F1-expressing cells in two-dimensional culture have cancer stem cell abilities and can form liver metastases in vivo. Single-cell RNA sequencing identifies heterogeneous populations derived from POU5F1-expressing cells and the Wnt signaling pathway is enriched in these cells.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yong Won Choi, Young Hwa Kim, Seung Yeop Oh, Kwang Wook Suh, Young-Sam Kim, Ga-Yeon Lee, Jung Eun Yoon, Soon Sang Park, Young-Kyoung Lee, Yoo Jung Park, Hong Seok Kim, So Hyun Park, Jang-Hee Kim, Tae Jun Park
Summary: Senescent tumor cells inhibit infiltration of CD8(+) T cells by secreting CXCL12 and enhancing differentiation of monocytes into M2 macrophages, forming a cytokine barrier to protect nonsenescent tumor cells. Targeting CXCL12 in senescent tumor cells could enhance T cell infiltration and reduce tumor size in CRC, providing a new strategy to overcome immunotherapy resistance.
Correction
Biotechnology & Applied Microbiology
Sergei Yakneen, Sebastian M. Waszak, Michael Gertz, Jan O. Korbel, Brice Aminou, Javier Bartolome, Keith A. Boroevich, Rich Boyce, Angela N. Brooks, Alex Buchanan, Ivo Buchhalter, Adam P. Butler, Niall J. Byrne, Andy Cafferkey, Peter J. Campbell, Zhaohong Chen, Sunghoon Cho, Wan Choi, Peter Clapham, Brandi N. Davis-Dusenbery, Francisco M. De La Vega, Jonas Demeulemeester, Michelle T. Dow, Lewis Jonathan Dursi, Juergen Eils, Roland Eils, Kyle Ellrott, Claudiu Farcas, Francesco Favero, Nodirjon Fayzullaev, Vincent Ferretti, Paul Flicek, Nuno A. Fonseca, Josep Ll. Gelpi, Gad Getz, Bob Gibson, Robert L. Grossman, Olivier Harismendy, Allison P. Heath, Michael C. Heinold, Julian M. Hess, Oliver Hofmann, Jongwhi H. Hong, Thomas J. Hudson, Barbara Hutter, Carolyn M. Hutter, Daniel Hubschmann, Seiya Imoto, Sinisa Ivkovic, Seung-Hyup Jeon, Wei Jiao, Jongsun Jung, Rolf Kabbe, Andre Kahles, Jules N. A. Kerssemakers, Hyung-Lae Kim, Hyunghwan Kim, Jihoon Kim, Youngwook Kim, Kortine Kleinheinz, Michael Koscher, Antonios Koures, Milena Kovacevic, Chris Lawerenz, Ignaty Leshchiner, Jia Liu, Dimitri Livitz, George L. Mihaiescu, Sanja Mijalkovic, Ana Mijalkovic Lazic, Satoru Miyano, Naoki Miyoshi, Hardeep K. Nahal-Bose, Hidewaki Nakagawa, Mia Nastic, Steven J. Newhouse, Jonathan Nicholson, Brian D. O'Connor, David Ocana, Kazuhiro Ohi, Lucila Ohno-Machado, Larsson Omberg, B. F. Francis Ouellette, Nagarajan Paramasivam, Marc D. Perry, Todd D. Pihl, Manuel Prinz, Montserrat Puiggros, Petar Radovic, Keiran M. Raine, Esther Rheinbay, Mara Rosenberg, Romina Royo, Gunnar Ratsch, Gordon Saksena, Matthias Schlesner, Solomon I. Shorser, Charles Short, Heidi J. Sofia, Jonathan Spring, Lincoln D. Stein, Adam J. Struck, Grace Tiao, Nebojsa Tijanic, David Torrents, Peter Van Loo, Miguel Vazquez, David Vicente, Jeremiah A. Wala, Zhining Wang, Sebastian M. Waszak, Joachim Weischenfeldt, Johannes Werner, Ashley Williams, Youngchoon Woo, Adam J. Wright, Qian Xiang, Liming Yang, Denis Yuen, Christina K. Yung, Junjun Zhang, Jan O. Korbel
NATURE BIOTECHNOLOGY
(2023)
Article
Cell & Tissue Engineering
Ruzhica Bogeska, Ana-Matea Mikecin, Paul Kaschutnig, Malak Fawaz, Marleen Buechler-Schaeff, Duy Le, Miguel Ganuza, Angelika Vollmer, Stella Paffenholz, Noboru Asada, Esther Rodriguez-Correa, Felix Frauhammer, Florian Buettner, Melanie Ball, Julia Knoch, Sina Staeble, Dagmar Walter, Amelie Petri, Martha J. Carreno-Gonzalez, Vinona Wagner, Benedikt Brors, Simon Haas, Daniel B. Lipka, Marieke A. G. Essers, Vivienn Weru, Tim Holland-Letz, Jan-Philipp Mallm, Karsten Rippe, Stephan Kraemer, Matthias Schlesner, Shannon McKinney Freeman, Maria Carolina Florian, Katherine Y. King, Paul S. Frenette, Michael A. Rieger, Michael D. Milsom
Summary: Infection or inflammation may lead to irreversible depletion of functional hematopoietic stem cells, resulting in long-term effects on tissue maintenance and regeneration.
Article
Multidisciplinary Sciences
Lino Moehrmann, Maximilian Werner, Malgorzata Oles, Andreas Mock, Sebastian Uhrig, Arne Jahn, Simon Kreutzfeldt, Martina Froehlich, Barbara Hutter, Nagarajan Paramasivam, Daniela Richter, Katja Beck, Ulrike Winter, Katrin Pfuetze, Christoph E. Heilig, Veronica Teleanu, Daniel B. Lipka, Marc Zapatka, Dorothea Hanf, Catrin List, Michael Allgaeuer, Roland Penzel, Gina Ruter, Ivan Jelas, Rainer Hamacher, Johanna Falkenhorst, Sebastian Wagner, Christian H. Brandts, Melanie Boerries, Anna L. Illert, Klaus H. Metzeler, C. Benedikt Westphalen, Alexander Desuki, Thomas Kindler, Gunnar Folprecht, Wilko Weichert, Benedikt Brors, Albrecht Stenzinger, Evelin Schroeck, Daniel Huebschmann, Peter Horak, Christoph Heining, Stefan Froehling, Hanno Glimm
Summary: We conducted comprehensive molecular characterization of 70 patients with cancer of unknown primary and identified substantial mutational heterogeneity and commonly mutated cancer-related genes. Our data demonstrate the clinical value of molecular analysis and recommend off-label therapy for a subset of patients, resulting in improved progression-free survival.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Carolin Andresen, Tobias Boch, Hagen M. Gegner, Nils Mechtel, Andreas Narr, Emrullah Birgin, Erik Rasbach, Nuh Rahbari, Andreas Trumpp, Gernot Poschet, Daniel Huebschmann
Summary: This study compares ten extraction protocols in four human sample types to detect and quantify different metabolites. The results show that extraction efficiency and repeatability vary across protocols, tissues, and chemical classes of metabolites. The coverage of extracted metabolites depends on the solvents used, which has implications for measuring different sample types and metabolic compounds of interest.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Dania Riegel, Elena Romero-Fernandez, Malte Simon, Akinbami Raphael Adenugba, Katrin Singer, Roman Mayr, Florian Weber, Mark Kleemann, Charles D. Imbusch, Marina Kreutz, Benedikt Brors, Ines Ugele, Jens M. Werner, Peter J. Siska, Christian Schmidl
Summary: By integrating single-cell chromatin accessibility and RNA-seq data, we identified the heterogeneous functional and dysfunctional states of CD8+ tumor-infiltrating lymphocytes and revealed common chromatin remodeling and key regulatory factors involved in this process.
Article
Biochemistry & Molecular Biology
Julian Schroeter, Tal Dattner, Jennifer Huellein, Alejandra Jayme, Vincent Heuveline, Georg F. Hoffmann, Stefan Koelker, Dominic Lenz, Thomas Opladen, Bernt Popp, Christian P. Schaaf, Christian Staufner, Steffen Syrbe, Sebastian Uhrig, Daniel Huebschmann, Heiko Brennenstuhl
Summary: The use of high-throughput sequencing techniques is producing a large number of disease-associated variants and candidate genes. Integration of genetic, protein, functional, and conservation knowledge is necessary to assess their relevance and prioritize further studies. However, accessing the required information from different databases can be challenging, leading to reduced accessibility for potential users. Here, we present a standalone webtool called aRgus, which allows simple extraction and intuitive visualization of multi-layered gene, protein, variant, and variant effect prediction data, enabling timely assessment of protein regions vulnerable to variation and providing applications in variant interpretation and experimental design.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Oncology
C. Pixberg, M. Zapatka, M. Hlevnjak, S. Benedetto, J. P. Suppelna, J. Heil, K. Smetanay, L. Michel, C. Fremd, V Koerber, M. Ruebsam, L. Buschhorn, S. Heublein, B. Schaefgen, M. Golatta, C. Gomez, A. von Au, M. Wallwiener, S. Wolf, N. Dikow, C. Schaaf, E. Gutjahr, M. Allgaeuer, A. Stenzinger, K. Pfuetze, R. Kirsten, D. Huebschmann, H-P Sinn, D. Jaeger, A. Trumpp, R. Schlenk, T. Hoefer, V Thewes, A. Schneeweiss, P. Lichter
Summary: COGNITION is a diagnostic registry trial that aims to identify biomarkers in patients with early breast cancer who are at high risk for relapse. It utilizes genomic and transcriptomic profiling to guide targeted therapy after standard neoadjuvant chemotherapy. The concept offers novel therapy options and aims to increase cure rates for high-risk early breast cancer patients.
Article
Hematology
Elisa Donato, Nadia Correia, Carolin Andresen, Darja Karpova, Roberto Wuerth, Corinna Klein, Markus Sohn, Adriana Przybylla, Petra Zeisberger, Kathrin Rothfelder, Helmut Salih, Halvard Bonig, Sebastian Stasik, Christoph Roellig, Anna Dolnik, Lars Bullinger, Frank Buchholz, Christian Thiede, Daniel Huebschmann, Andreas Trumpp
Summary: This study proposes a novel flow cytometry sorting strategy for CD34 neg AML subtypes, enriching for leukemic stem cells (LSCs) independently of CD34 status by positive selection for GPR56 and negative selection for NKG2D ligands. The functional reconstitution capacity and transcriptomes of CD34- and CD34+ LSCs are shown to be similar, supporting the concept of phenotypic plasticity. Patients with AML who still retain functional hematopoietic stem cells (HSCs) at the time of diagnosis have longer relapse-free and overall survival.
Article
Oncology
Maria-Veronica Teleanu, Carmina T. Fuss, Nagarajan Paramasivam, Sebastian Pirmann, Andreas Mock, Christoph Terkamp, Stefan Kircher, Laura-Sophie Landwehr, Christina Lenschow, Nicolas Schlegel, Albrecht Stenzinger, Arne Jahn, Martin Fassnacht, Hanno Glimm, Daniel Huebschmann, Stefan Froehling, Matthias Kroiss
Summary: We performed whole-genome and RNA sequencing on four advanced parathyroid carcinoma patients to identify molecular alterations for clinical management. Two experimental therapies, immune checkpoint inhibition with pembrolizumab and multi-receptor tyrosine kinase inhibition with lenvatinib, showed promising results. Our data also provided new insights into the molecular landscape of parathyroid carcinoma.
MOLECULAR ONCOLOGY
(2023)
Article
Infectious Diseases
Fridolin Steinbeis, Charlotte Thibeault, Sarah Steinbrecher, Yvonne Ahlgrimm, Ira An Haack, Dietrich August, Beate Balzuweit, Carla Bellinghausen, Sarah Berger, Irina Chaplinskaya-Sobol, Oliver Cornely, Patrick Doeblin, Matthias Endres, Claudia Fink, Carsten Finke, Sandra Frank, Sabine Hanss, Tim Hartung, Johannes Christian Hellmuth, Susanne Herold, Peter Heuschmann, Jan Heyckendorf, Ralf Heyder, Stefan Hippenstiel, Wolfgang Hoffmann, Sebastian Ulrich Kelle, Philipp Knape, Philipp Koehler, Lucie Kretzler, David Manuel Leistner, Jasmin Lienau, Roberto Lorbeer, Bettina Lorenz-Depiereux, Constanze Dorothea Luettke, Knut Mai, Uta Merle, Lil Antonia Meyer-Arndt, Olga Miljukov, Maximilian Muenchhoff, Moritz Mueller-Plathe, Julia Neuhann, Hannelore Neuhauser, Alexandra Nieters, Christian Otte, Daniel Pape, Rafaela Maria Pinto, Christina Pley, Annett Pudszuhn, Philipp Reuken, Siegberg Rieg, Petra Ritter, Gernot Rohde, Maria Roennefarth, Michael Ruzicka, Jens Schaller, Anne Schmidt, Sein Schmidt, Verena Schwachmeyer, Georg Schwanitz, Werner Seeger, Dana Stahl, Nicole Stobaeus, Hans Christian Stubbe, Norbert Suttorp, Bettina Temmesfeld, Sylvia Thun, Paul Triller, Frederik Trinkmann, Istvan Vadasz, Heike Valentin, Maria Vehreschild, Christof von Kalle, Marie von Lilienfeld-Toal, Joachim Weber, Tobias Welte, Christian Wildberg, Robert Wizimirski, Saskia Zvork, Leif Erik Sander, Janne Vehreschild, Thomas Zoller, Florian Kurth, Martin Witzenrath
Summary: The NAPKON-HAP study is a multi-centered observational study aimed at providing comprehensive data and biospecimen collection for the investigation of the pathophysiology and pathology of COVID-19. It will contribute significant scientific insights and high-quality data to aid researchers in understanding the acute and long-term outcomes of the disease.
Article
Biochemical Research Methods
Zuguang Gu, Daniel Huebschmann
Summary: rGREAT is a new R/Bioconductor package that implements the GREAT algorithm locally, providing updated annotation data, support for numerous organisms and gene set collections, and extensibility for user customization.
Article
Genetics & Heredity
Zuguang Gu, Daniel Hubschmann Bschmann
Summary: Functional enrichment analysis is an important bioinformatics method for evaluating the biological importance of gene lists. The researchers proposed a new method called binary cut for clustering functional terms, which showed consistent similarities within clusters and exclusivity between clusters. They demonstrated the effectiveness of binary cut through comprehensive benchmarks on simulated and real-world datasets.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2023)
Article
Urology & Nephrology
Frederik Wessels, Max Schmitt, Eva Krieghoff-Henning, Malin Nientiedt, Frank Waldbillig, Manuel Neuberger, Maximilian C. Kriegmair, Karl-Friedrich Kowalewski, Thomas S. Worst, Matthias Steeg, Zoran V. Popovic, Timo Gaiser, Christof von Kalle, Jochen S. Utikal, Stefan Frohling, Maurice S. Michel, Philipp Nuhn, Titus J. Brinker
Summary: A interpretable deep learning model, DINO-ViT, was developed and validated to predict overall and disease-specific survival in ccRCC. The model achieved significant risk stratification and showed good interpretability by extracting image features from nuclei, cytoplasm, and peritumoural stroma.
WORLD JOURNAL OF UROLOGY
(2023)
Article
Hematology
Cristina Lopez, Nikolai Schleussner, Stephan H. Bernhart, Kortine Kleinheinz, Stephanie Sungalee, Henrike L. Sczakiel, Helene Kretzmer, Umut H. Toprak, Selina Glaser, Rabea Wagener, Ole Ammerpohl, Susanne Bens, Maciej Giefing, Juan C. Gonzalez Sanchez, Gordana Apic, Daniel Huebschmann, Martin Janz, Markus Kreuz, Anja Mottok, Judith M. Mueller, Julian Seufert, Steve Hoffmann, Jan O. Korbel, Robert B. Russell, Roland Schuele, Lorenz Truemper, Wolfram Klapper, Bernhard Radlwimmer, Peter Lichter, Ralf Kueppers, Matthias Schlesner, Stephan Mathas, Reiner Siebert
Summary: Histone methylation-modifiers, including EZH2 and KMT2D, are frequently altered in B-cell lymphomas. In this study, we examined the whole genome and transcriptome data of 186 cases and identified recurrent alterations in KDM4C, a histone demethylase encoding gene on chromosome 9p24. We demonstrated that these structural variants in KDM4C result in loss-of-function and provide evidence that KDM4C can act as a tumor suppressor. Thus, our findings expand the mutational landscape of lymphomas and highlight the importance of KDM4C in B-cell derived lymphomas.
Article
Oncology
Edwin Cuppen, Olivier Elemento, Richard Rosenquist, Svetlana Nikic, Maarten IJzerman, Isabelle Durand Zaleski, Geert Frederix, Lars-Ake Levin, Charles G. Mullighan, Reinhard Buettner, Trevor J. Pugh, Sean Grimmond, Carlos Caldas, Fabrice Andre, Ilse Custers, Elias Campo, Hans van Snellenberg, Anna Schuh, Hidewaki Nakagawa, Christof von Kalle, Torsten Haferlach, Stefan Froehling, Vaidehi Jobanputra
Summary: The combination of whole-genome and transcriptome sequencing (WGTS) is a comprehensive precision diagnostic test that is expected to transform diagnosis and treatment for cancer patients. However, there are barriers to the implementation and widespread adoption of this test, including considerations of utility in different cancer types, cost-effectiveness and affordability.
JCO PRECISION ONCOLOGY
(2022)
