tbuckley/cabot-search huggingface dataset:
Association of Hospital Flagship System Affiliation on Surgical Outcomes Following Complex Cancer Surgery
Authors: Muhammad Musaab Munir, Mujtaba Khalil, Muhammad Muntazir Mehdi Khan, Selamawit Woldesenbet, Mary Dillhoff, Susan Tsai, Timothy M. Pawlik
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: We evaluated variations in patient outcomes and financial expenditures following complex cancer surgery across flagship hospitals and their affiliates. Methods: Using Medicare 100% Standard Analytic Files (2018–2021), we identified patients undergoing resection of lung, esophageal, gastric, hepatopancreatobiliary, or colorectal cancer. Flagship hospitals were defined as the highest-volume major teaching hospital within a system in each region. Propensity score matching was performed to create a 1:1 matched cohort to assess the association between flagship systems, hospitals, affiliates, and outcomes. Results: Among 110,670 patients, 55,335 treated within a flagship hospital system (median age, 73 years [IQR, 69–79]; including 29,381 [53.1%] women) were matched with 55,335 patients who were not (median age, 73 years [IQR, 69–79]; including 29,274 [52.9%] women) across 35 regions. Patients at flagship system hospitals had lower 30-day mortality rates than matched controls (4.23% vs 4.88%; difference, −0.65% [95% CI, −0.89% to −0.40%]; P &lt;.001). Mortality was also lower at flagship hospitals (2.76% vs 3.82%; difference, −1.06% [95% CI, −1.62% to −0.50%]) and flagship affiliates (4.46% vs 4.79%; difference, −0.32% [95% CI, −0.58 to −0.07]) compared with controls (both P &lt;.001). However, patients who underwent cancer surgery at flagship hospital systems had higher expenditures ($21,011 vs $20,016; difference, +$995 [95% CI, $797 to $1,193]; P &lt;.001). Conclusions: Flagship hospitals are the primary drivers of decreased postoperative mortality following complex oncologic surgical procedures performed within their systems, although expenditures were higher compared with unaffiliated hospitals.
NCCN Guidelines® Insights: Multiple Myeloma, Version 1.2025
Authors: Shaji K. Kumar, Natalie S. Callander, Kehinde Adekola, Larry D. Anderson, Muhamed Baljevic, Rachid Baz, Erica Campagnaro, Caitlin Costello, Christopher D’Angelo, Benjamin Derman, Srinivas Devarakonda, Noura Elsedawy, Amandeep Godara, Kelly Godby, Jens Hillengass, Leona Holmberg, Myo Htut, Carol Ann Huff, Malin Hultcrantz, Yubin Kang, Sarah Larson, Hans C. Lee, Michaela Liedtke, Thomas Martin, James Omel, Timothy Robinson, Aaron Rosenberg, Mark A. Schroeder, Daniel Sherbenou, Attaya Suvannasankha, Jason Valent, Asya Nina Varshavsky-Yanovsky, Dan Vogl, Emily Kovach, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2025)

The NCCN Guidelines for Multiple Myeloma (MM) provide recommendations for diagnosis, initial workup, treatment, follow-up, and supportive care for patients with MM. These NCCN Guidelines Insights highlight the important updates and changes specific to systemic therapy for patients with newly diagnosed as well as previously treated MM included in Version 1.2025 of the NCCN Guidelines for MM.
Machine Learning-Enabled Screening for Aortic Stenosis with Handheld Ultrasound
Authors: Samuel Karmiy, Zhe Huang, Divya Velury, Eileen Mai, Jing Li, Monica M Dehn, Dikran R Balian, Davinder Ramsingh, John Martin, Jacob Kantrowitz, Ayan R Patel, Michael C Hughes, Benjamin S Wessler
Journal:  (2025)

Abstract Aims Neural network classifiers can detect aortic stenosis (AS) using limited cardiac ultrasound images. While networks perform very well using cart-based imaging, they have never been tested or fine-tuned for use with focused cardiac ultrasound (FoCUS) acquisitions obtained on handheld ultrasound devices. Methods and results Prospective study performed at Tufts Medical Center. All patients ≥65 years of age referred for clinically indicated transthoracic echocardigraphy (TTE) were eligible for inclusion. Parasternal long axis and parasternal short axis imaging was acquired using a commercially available handheld ultrasound device. Our cart-based AS classifier (trained on ∼10 000 images) was tested on FoCUS imaging from 160 patients. The median age was 74 (inter-quartile range 69–80) years, 50% of patients were women. Thirty patients (18.8%) had some degree of AS. The area under the received operator curve (AUROC) of the cart-based model for detecting AS was 0.87 (95% CI 0.75–0.99) on the FoCUS test set. Last-layer fine-tuning on handheld data established a classifier with AUROC of 0.94 (0.91–0.97). AUROC during temporal external validation was 0.97 (95% CI 0.89–1.0). When performance of the fine-tuned AS classifier was modelled on potential screening environments (2 and 10% AS prevalence), the positive predictive value ranged from 0.72 (0.69–0.76) to 0.88 (0.81–0.97) and negative predictive value ranged from 0.94 (0.94–0.94) to 0.99 (0.99–0.99) respectively. Conclusion Our cart-based machine-learning model for AS showed a drop in performance when tested on handheld ultrasound imaging collected by sonographers. Fine-tuning the AS classifier improved performance and demonstrates potential as a novel approach to detecting AS through automated interpretation of handheld imaging.
ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte development
Authors: Yu-Ke Wu, Ruibao Su, Zhi-Yan Jiang, Yun-Wen Wu, Yan Rong, Shu-Yan Ji, Jingwen Liu, Zhuoyue Niu, Zhiyi Li, Yuanchao Xue, Falong Lu, Heng-Yu Fan
Journal: Genome biology (2025)

During meiosis, the oocyte genome keeps dormant for a long time until zygotic genome activation. The dynamics and homeostasis of the maternal transcriptome are essential for maternal-to-zygotic transition. Zygotic arrest 1 (ZAR1) and its homolog, ZAR2, are RNA-binding proteins that are important for the regulation of maternal mRNA stability. Smart-seq2 analysis reveals drastically downregulated maternal transcripts. However, the detection of transcript levels by Smart-seq2 may be biased by the polyadenylated tail length of the mRNAs. Similarly, differential expression of maternal transcripts in oocytes with or without Zar1/2 differs when analyzed using total RNA-seq and Smart-seq2, suggesting an influence of polyadenylation. Combined analyses using total RNA-seq, LACE-seq, PAIso-seq2, and immunoprecipitation-mass spectrometry reveals that ZAR1 may target the 3'-untranslated regions of maternal transcripts, regulates their stability in germinal vesicle stage oocytes, and interacts with other proteins to control the polyadenylation of mRNAs. The jointly analyzed multi-omics data highlight the limitations of Smart-seq2 in oocytes, clarify the dynamics of the maternal transcriptome, and uncover new roles of ZAR1 in regulating the maternal transcriptome.
Epigenome profiling reveals distinctive regulatory features and cis-regulatory elements in pepper
Authors: Hongji Yang, Guorong Yu, Zhidong Lv, Tonghui Li, Xi Wang, Ying Fu, Zhangsheng Zhu, Guangjun Guo, Hang He, Ming Wang, Guochen Qin, Feng Liu, Zhenhui Zhong, Yan Xue
Journal: Genome biology (2025)

Pepper (Capsicum annuum) is one of the earliest and most widely cultivated vegetable crops worldwide. While the large and complex genome of pepper severely hampered the understanding of its functional genome, it also indicates a rich yet unexplored reservoir of regulatory elements (REs). In fact, variations in the REs represent a major driving force in evolution and domestication in both plants and animals. However, identification of the REs remains difficult especially for plants with complex genomes. Here, we present a comprehensive epigenomic landscape of Capsicum annuum, Zhangshugang (ST-8), including chromatin accessibility, histone modifications, DNA methylation, and transcriptome. We also develop comparative crosslinked immunoprecipitation mass spectrometry to reveal the proteome associated with certain chromatin features. Through integrated analysis of these epigenetic features, we profile promoters and enhancers involved in development, heat stress and cucumber mosaic virus challenges. We generate stress responsive expression networks composed of potential transcription activators and their target genes. Through population genetics analysis, we demonstrate that some regulatory elements show lower nucleotide diversity compare to other genomic regions during evolution. We demonstrate that variations in the REs may contribute to more diversified and agronomically desired phenotypes. Our study provides a foundation not only for studying gene regulation, but also for targeted genetic and epigenetic manipulation for pepper improvement.
FRI-166 Real-world evidence on clinical outcomes and microbiome changes after healthy donor stool transplantation as palliative therapy compared to best supportive care in patients with unstable decompensations in alcohol-related end-stage liver disease
Authors: Cyriac Philips, Arif Theruvath, Rizwan Ahamed, Tharun Oommen, Nibin Nahaz, Ajit Tharakan, Philip Augustine
Journal: Journal of Hepatology (2025)
FRI-086-YI Long-term survival outcomes in patients receiving atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma: an update of the AB-real study
Authors: Bernardo Stefanini, Leonardo Brunetti, Pasquale Lombardi, Bernhard Scheiner, Matthias Pinter, Hong Jae Chon, Linda Wu, Celina Ang, Anwaar Saeed, Lorenza Rimassa, Giulia Tesini, Masatoshi Kudo, Naoshi Nishida, Pei-Chang Lee, Yi-Hsiang Huang, Wei-Fan Hsu, Gianluca Masi, Arndt Vogel, Amit Singal, Martin Schoenlein, Johann von Felden, Peter R. Galle, Giulia Francesca Manfredi, Neehar D. Parikh, Alessandro Parisi, Natascha Röhlen, Yehia Abugabal, Ahmed Kaseb, Andrea Dalbeni, Brooke Wietharn, Ciro Celsa, Giuseppe Cabibbo, Changhoon Yoo, Francesco Tovoli, Antonio D’Alessio, Fabio Piscaglia, David J. Pinato
Journal: Journal of Hepatology (2025)
OS-031-YI Hepatocyte-neutrophil interaction in the liver via SAA-FPR2 is key in the pathogenesis of alcohol-associated hepatitis
Authors: Alicia Martínez-Álvarez, Aina Rill, Jordi Gratacós-Ginès, Alex Guillamon-Thiery, Raquel Ferrer-Lorente, Silvia Ariño, Martina Perez-Guasch, Ana Belén Rubio, Celia Martinez-Sanchez, Laia Aguilar-Corominas, Xènia Almodòvar, Pau Sancho-Bru, Ramon Bataller, Pere Ginès, Elisabetta Mereu, Mar Coll, Elisa Pose
Journal: Journal of Hepatology (2025)
THU-115-YI Targeting UBE2I-mediated protein hyper-SUMOylation halts cholangiocarcinoma progression and rewires the tumor-stroma crosstalk
Authors: Irene Olaizola, Paula Olaizola, Marta Fernandez de Ara, Ainhoa Lapitz, Laura Izquierdo-Sánchez, Maite G Fernandez-Barrena, Laura Alvarez, Colm O Rourke, Pui-Yuen Lee-Law, Kyle Davies, Andreea Gradinaru, Raul Jimenez-Aguero, Adelaida La Casta, Ioana Riaño, Rocio Macias, Jose Marin, María Luz Martínez-Chantar, Matías A Avila, Patricia Aspichueta, Jesper Andersen, Luke Boulter, Luis Bujanda, Pedro Miguel Rodrigues, Maria Jesus Perugorria, Jesus Maria Banales
Journal: Journal of Hepatology (2025)
WED-097 Identification of diagnostic markers based on spectral infrared fingerprints of bile samples from endoscopic drainage of patients with biliary stenosis due to extrahepatic cholangiocarcinoma or pancreatic adenocarcinoma
Authors: Solene Adam, Valérie Untereiner, Roselyne Garnotel, Gerard Thiefin, Ganesh Sockalingum, Elia Gigante
Journal: Journal of Hepatology (2025)
WED-398 Bone fragility and fracture risk assessment in metabolic disfunction-associated steatotic liver disease
Authors: Clelia Asero, Cecilia Oliveri, Maria Stella Franze, Adele Di Giovanni, Roberto Filomia, Gaia Caccamo, Concetta Pitrone, Carlo Saitta, Carmela Morace, Nunziata Morabito, Giorgio Basile, Antonino Catalano, Irene Cacciola
Journal: Journal of Hepatology (2025)
THU-144 Epigenetic regulation of LSECtin in hepatic antigen presenting cells during experimental cirrhosis
Authors: Enrique Ángel-Gomis, Sebastián Martínez-López, Isabel Gómez-Hurtado, Paula Boix, Oriol Juanola, Maite G. Fernandez-Barrena, Manel Hadid, Matías A. Avila, Esther Caparrós, Rubén Francés
Journal: Journal of Hepatology (2025)
SAT-482-YI Prospective study of phosphatidylethanol as a quantitative, objective biomarker to detect under-reported alcohol use in steatotic liver disease
Authors: Federica Tavaglione, Luis Antonio Diaz, Monica Tincopa, Veeral Ajmera, Maral Amangurbanova, Egbert Madamba, Seema Singh, Ricki Bettencourt, Lisa Richards, Claude Sirlin, Rohit Loomba
Journal: Journal of Hepatology (2025)
FRI-302-YI MUCIN1 positive biliary epithelial cell heterogeneity contributes to cholestatic liver injury and promotes early liver fibrosis
Authors: Aishwarya Bhatnagar, Rajni Yadav, Himanshi Himanshi, Vaibhav Tiwari, Tahseen Khan, Chhagan Bihari, Savneet Kaur, Shiv Kumar Sarin, Dinesh Mani Tripathi
Journal: Journal of Hepatology (2025)
TOP-052-YI Baseline oral microbiome composition in liver transplant recipients can help predict graft dysfunction
Authors: Rosmy Babu, Manjeet Kaur, Shvetank Sharma, Sukriti Baweja, Jaswinder Maras, Satender Pal Singh, Nilesh Patil, Archana Rastogi, Viniyendra Pamecha, Shiv Kumar Sarin, Chhagan Bihari
Journal: Journal of Hepatology (2025)
FRI-178 Development of an AI-driven predictive model and decision support system for managing acute-on-chronic liver failure: insights from the KACLiF cohort
Authors: Seong Hee Kang, Hyung Joon Yim, Young Kul Jung, Do Seon Song, Eileen Yoon, Won Kim, Jae Young Jang, Dong Joon Kim
Journal: Journal of Hepatology (2025)
FRI-164 Efficacy of Granulocyte Colony-stimulating factor in hepatitis B virus-associated acute-on-chronic liver failure patients: a multicenter study
Authors: Jing Yuan, Jing Chen, Haibin Su, Yu Chen, Tao Han, Tao Chen, Xiaoyan Liu, Qi Wang, Pengbin Gao, Jinjun Chen, Jingjing Tong, Chen Li, Jinhua Hu
Journal: Journal of Hepatology (2025)
FRI-064 MicroRNA-122 functions as a rheostat regulating liver tolerance, inflammation and fibrosis
Authors: Maytal Gefen, Shanny Layani, Emma Klahr, Zohar Shemuelian, Johannes Brandi, Thomas Jacobs, Christiane Steeg, Lorenz Adlung, Christoph Kilian, Merav Ordan, Oren Gordon, Nathalie Abudi, Rinat Abramovitch, Yuval Nevo, Shrona Elgavish, Hadar Benyamini, Jonathan Monin, Elina Zorde-Khavlevsky, Nofar Rosenberg, Aurelia Markezana, Dayana Yaish, Adi Sheena Yehezkel, Alina Simerzin, Mila Rivkin, Osher Amran, Daniel Goldenberg, Amnon Peled, Jonathan Axelrod, Jacob Rachmilewitz, Samuel Huber, Nicola Gagliani, Christoph Schramm, Sören Alexander Weidemann, Johannes Herkel, Antonella Carambia, Rifaat Safadi, Abed Khakayla, Achraf Imam, Danijela Heide, Jenny Hetzer, Stefan Rose-John, Mathias Heikenwälder, Hilla Giladi, Eithan Galun
Journal: Journal of Hepatology (2025)
FRI-149 Serum levels of immune checkpoints in drug-induced liver injury and metabolic dysfunction-associated steatotic liver disease
Authors: Juan Pedro Toro Ortiz, Jose Pinazo Bandera, Alberto García-García, Mercedes Robles-Díaz, Aida Ortega-Alonso, Enrique del Campo Herrera, Gonzalo Matilla-Cabello, Antonio Segovia-Zafra, Marina Villanueva, Daniel E. Di Zeo-Sánchez, Maria Isabel Lucena, Raul J. Andrade, Eduardo García-Fuentes, Miren Garcia Cortes
Journal: Journal of Hepatology (2025)
SAT-464 Prospective evaluation of undiagnosed MetALD prevalence in MASLD patients using the ani score
Authors: Carlos Alventosa-Mateu, Mercedes Latorre Sánchez, Inmaculada Castelló Miralles, Alejandro Fernández Soro, Lara González González, José David Prieto Climent, Benjamín Climent Díaz, Moises Diago, Juan José Urquijo Ponce
Journal: Journal of Hepatology (2025)
OS-083 Inhibition of the CCR9-CCL25 axis improves the visceral fat environment and ameliorates liver steatosis
Authors: Ryosuke Kasuga, Nobuhiro Nakamoto, Yukie Nakadai, Haruka Okada, Takaya Tabuchi, Nobuhito Taniki, Shingo Usui, Keisuke Ojiro, Takanori Kanai
Journal: Journal of Hepatology (2025)
LBP-021 Prolonged reduction of hepatitis B surface antigen in virologically suppressed participants treated with concurrent or sequential use of pegylated interferon alpha with xalnesiran-based therapy: results after 120 weeks of follow-up of an observational study
Authors: Xieer Liang, Zhihong Liu, Qintao Lai, Jie Peng, Aili Lu, Juanjuan Chen, Farouk Chughlay, Qingyan Bo, Cong Cheng, Jinlin Hou
Journal: Journal of Hepatology (2025)
LBP-009 Globally derived and externally validated cut offs for liver failure and inclusion of infections improve prognostication for inpatient death: towards ACLF harmonization
Authors: Jasmohan Bajaj, Scott Silvey, Aidan Mullan, Ashok Choudhury, Florence Wong, Mark Topazian, Ramazan Idilman, Mario Álvares-da-Silva, Aldo Torre, Qing Xie, Peter Hayes, Wai-Kay Seto, Hailemichael Desalegn, Jacob George, Brian Bush, Patrick S. Kamath
Journal: Journal of Hepatology (2025)
THU-485 Prevalence, genetic risks, and cardiovascular outcomes of Met-ALD in a longitudinal multiethnic U.S. cohort
Authors: Jie Yao, Xiuqing Guo, Jingyi Tan, Callie Zaborenko, Marco Abreu, Tae-Hwi Linus Schwantes-An, Matt Budoff, Mariana Lazo, Jerome Rotter, Naga Chalasani
Journal: Journal of Hepatology (2025)
OS-048 Mucosal-associated invariant T cells promote liver regeneration
Authors: Charles Caer, Quanyu Chen, Manon Allaire, Marc-Anthony Chouillard, Hammoutene Adel, Al Sayegh Rola, JingHong Wan, Olivier Lantz, Emmanuel Weiss, Valerie Paradis, Sophie Lotersztajn, Hélène Gilgenkrantz
Journal: Journal of Hepatology (2025)
THU-425-YI Clinical and genetic predictors of steatotic liver disease in lean individuals: a cohort study of risk factors and fibrosis prediction
Authors: Angela Sato Espinoza, Filippo Pinto e Vairo, Perapa Chotiprasidhi, Shulan Tian, Robert Vierkant, Jun Ma, Daniel O’Brien, Konstantinos N. Lazaridis, Alina M. Allen, Kirk Wangensteen
Journal: Journal of Hepatology (2025)
THU-153 Immunometabolism of mononuclear cells from blood and ascites in patients with decompensated cirrhosis: compartment-specific features of metabolic dysfunction
Authors: Hasan Tarik Cosgun, Pavitra Kumar, Linda Hammerich, Ingrid Wei Zhang, Virein Sudheer, Charalampos Pavlidis, Hannah Schwarz, Juan Wang, Frank Tacke, Ali Canbay, Cornelius Engelmann
Journal: Journal of Hepatology (2025)
WED-083 Role of Child-Turcotte-Pugh and ALBI scores in patients with non-cirrhotic hepatocellular carcinoma
Authors: Abelina Kreuter, Leonardo Brunetti, Lorenz Balcar, Claudia Fulgenzi, Tobias Meischl, Antonio D’Alessio, Katharina Pomej, Jaekyung Cheon, Naoshi Nishida, Pei-Chang Lee, Linda Wu, Celina Ang, Anja Krall, Anwaar Saeed, Bernardo Stefanini, Antonella Cammarota, Tiziana Pressiani, Yehia Abugabal, Shadi Chamseddine, Brooke Wietharn, Alessandro Parisi, Yi-Hsiang Huang, Samuel Phen, Caterina Vivaldi, Francesca Salani, Gianluca Masi, Natascha Röhlen, Arndt Vogel, Johann von Felden, Kornelius Schulze, Marianna Silletta, Michael Trauner, Adel Samson, Henning Wege, Fabio Piscaglia, Peter R. Galle, Rudolf Stauber, Masatoshi Kudo, Amit Singal, Haripriya Andanamala, Susanna V. Ulahannan, Neehar D. Parikh, Alessio Cortellini, Ahmed Kaseb, Lorenza Rimassa, Hong Jae Chon, Ciro Celsa, Ashwini Arvind, Michael Li, Giulia Manfredi, Giuseppe Cabibbo, Katie Kelley, Paul El Tomb, Bernhard Scheiner, David J. Pinato, Matthias Pinter
Journal: Journal of Hepatology (2025)
FRI-193 A machine-learning algorithm using real-world data identified subpopulations at risk for adverse outcomes in patients with acute-on-chronic liver failure
Authors: Jonel Trebicka, Arun J. Sanyal, Thierry Artzner, William Bernal, Joan Clària, Javier Fernández, Lise Lotte Gluud, Jennifer Lai, Jacqueline O’Leary, Pierre-Emmanuel Rautou, Debbie L. Shawcross, Bart Staels, Florence Wong, Carol Addy, Stephanie Ferreira, Dean Hum, Jeremy Magnanensi, Pierbruno Ricci, Katharina Staufer, Richard Moreau, Paolo Angeli, Jasmohan Bajaj
Journal: Journal of Hepatology (2025)
THU-244 Tissue virological response is the main predictor of hepatitis D relapses
Authors: Pavel Bogomolov, Maria Arapova, Natalia Barsukova, Alexander Demyanov, Nadezhda Shub, Alexey Bueverov, Ekaterina Isaeva, Sergei Koblov, Michail Kalashnikov, Natalia Gasilova, Anna Belyakova, Cagan Lidzhieva, Elena Kondrashеva
Journal: Journal of Hepatology (2025)
THU-173 A biliary organoid model to investigate the malignant transformation of primary sclerosing cholangitis to cholangiocarcinoma
Authors: Lea Allescher, Noah Sendtner, Noah Brandl, Manuela Gunckel, Kunst Claudia, Karsten Guelow, Martina Müller-Schilling, Arne Kandulski
Journal: Journal of Hepatology (2025)
FRI-197 The AMMON-OHE model predicts liver-related complications in outpatients with cirrhosis: a prospective cohort study of the AMMON consortium
Authors: María Pilar Ballester, Lorenz Balcar, Thomas Tranah, Paloma Poyatos-García, Jose Sanchez-Serrano, Juan José Gallego Roig, Javier Ampuero Herrojo, Karen Louise Thomsen, Desamparados Escudero-García, Salvador Benlloch, Carmina Montoliu, Thomas Reiberger, Debbie L. Shawcross, Manuel Romero-Gómez, Mattias Mandorfer, Rajiv Jalan, Juan Antonio Carbonell-Asins
Journal: Journal of Hepatology (2025)
OS-052 Chronic exposure to microplastics and nanoplastics exacerbates western diet-induced metabolic dysfunction-associated steatohepatitis: the role of gut microbiota
Authors: Dekai Zheng, Changhao Cheng, Zhixin Fang, Xuelian Gao, Kaikai Zhang, Yuchuan Chen, Heqi Zhou, Xun Wang, Routing Wang, Zhixian Lan, Yanhua Tang, Jian Sun
Journal: Journal of Hepatology (2025)
DNA methylation epitypes of Burkitt lymphoma with distinct molecular and clinical features
Authors: Nicole Thomas, Carlos A. García-Prieto, Kostiantyn Dreval, Laura K. Hilton, Jeremy S. Abramson, Nancy L. Bartlett, Jeffrey Bethony, Jay Bowen, Anthony C. Bryan, Corey Casper, Maureen A. Dyer, Julie M. Gastier-Foster, Alina S. Gerrie, Timothy C. Greiner, Nicholas B. Griner, Thomas G. Gross, Nancy Harris, John D. Irvin, Elaine S. Jaffe, Fabio E. Leal, Sam M. Mbulaiteye, Charles G. Mullighan, Andrew J. Mungall, Karen L. Mungall, Constance Namirembe, Ariela Noy, Martin D. Ogwang, Jackson Orem, German Ott, Hilary Petrello, Steven J. Reynolds, Steven H. Swerdlow, Alexandra Traverse-Glehen, Wyndham H. Wilson, Marco A. Marra, Louis M. Staudt, David W. Scott, Manel Esteller, Ryan D. Morin
Journal: Blood Cancer Discovery (2025)

Abstract The genetic subtypes of Burkitt Lymphoma (BL) have been defined, whereas the role of epigenetics remains to be comprehensively characterized. We searched genomic DNA from 218 patients across four continents, for recurrent DNA methylation patterns and their associations with clinical and molecular features. We identified DNA methylation patterns that were not fully explained by EBV status or mutation status, leading to two epitypes, described here as HypoBL and HyperBL. Each is characterized by distinct genomic and clinical features including global methylation, mutation burden, aberrant somatic hypermutation, and survival outcomes. Methylation, gene expression and mutational differences between the epitypes support a model in which each arises from a distinct cell-of-origin. These results, pending validation in external cohorts, point to a refined risk assessment for BL patients who may experience inferior outcomes.