Article
Critical Care Medicine
Hongsheng Gui, Albert M. Levin, Donglei Hu, Patrick Sleiman, Shujie Xiao, Angel C. Y. Mak, Mao Yang, Andrea J. Barczak, Scott Huntsman, Celeste Eng, Samantha Hochstadt, Ellen Zhang, Kyle Whitehouse, Samantha Simons, Whitney Cabral, Sami Takriti, Goncalo Abecasis, Thomas W. Blackwell, Hyun Min Kang, Deborah A. Nickerson, Soren Germer, David E. Lanfear, Frank Gilliland, W. James Gauderman, Rajesh Kumar, David J. Erle, Fernando D. Martinez, Hakon Hakonarson, Esteban G. Burchard, L. Keoki Williams
Summary: This study identified a functional variant at the 17q12-21.1 locus associated with early-onset asthma in African American individuals. The lead signal, rs11078928, was found to be the top association for early-onset asthma after meta-analysis across cohorts. Additionally, a haplotype analysis suggested that the asthma association most closely with this variant.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2021)
Article
Gastroenterology & Hepatology
Fanny E. R. Vuik, Stella A. Nieuwenburg, Iris D. Nagtegaal, Ernst J. Kuipers, Manon C. W. Spaander
Summary: The study found that younger patients were more likely to have signet-ring cells and poorly differentiated tumors, as well as a higher risk of lymph node metastases. Over time, there was an increase in the proportion of colorectal cancers diagnosed in women, especially in the younger age group.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Multidisciplinary Sciences
Yinci Zhang, Xinkuang Liu, Amin Li, Xiaolong Tang
Summary: This study conducted a pan-cancer analysis of the most commonly mutated gene in colon cancer, APC, and found that APC is not only associated with colorectal neoplasms but also with other cancer types such as breast cancer. APC is low expressed in most tumors, and its expression is correlated with the pathological stages, survival, and prognosis of tumor patients. Additionally, APC expression is associated with immune cell infiltration and cancer-associated fibroblast infiltration.
Article
Oncology
Satu Maki-Nevala, Sanjeevi Ukwattage, Alisa Olkinuora, Henrikki Almusa, Maarit Ahtiainen, Ari Ristimaki, Toni Seppala, Anna Lepisto, Jukka-Pekka Mecklin, Paivi Peltomaki
Summary: Ulcerative colitis increases the risk of colorectal cancer, and this study examined the genetic and epigenetic profiles of colitis-associated colorectal carcinomas (CA-CRC). Subgroups within CA-CRC were identified with different mutational loads and signatures, which may guide clinical management and therapy options. Lynch syndrome tumors showed a higher degree of hypermutability compared to CA-CRC subgroups.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Oncology
Andreana N. Holowatyj, Wanqing Wen, Timothy Gibbs, Hannah M. Seagle, Samantha R. Keller, Digna R. Velez Edwards, Mary K. Washington, Cathy Eng, Jose Perea, Wei Zheng, Xingyi Guo
Summary: This study investigated somatic mutation patterns in colorectal cancer patients of different races/ethnicities and sexes, finding that non-Hispanic Black and Asian/Pacific Islander patients with early-onset nonhypermutated colorectal cancer had higher tumor mutation rates compared to non-Hispanic white patients. Significant differences were observed in the mutation frequencies of several genes between racial/ethnic groups in early-onset nonhypermutated colorectal cancers. Furthermore, heterogeneity was observed in the effects of certain genes between early-onset and late-onset nonhypermutated colorectal cancer, as well as between males and females. These findings provide important insights into the genomic patterns and disparities of early-onset colorectal cancer based on race/ethnicity and sex.
Article
Oncology
Mariano Golubicki, Marcos Diaz-Gay, Laia Bonjoch, Sebastia Franch-Exposito, Jenifer Munoz, Miriam Cuatrecasas, Teresa Ocana, Soledad Iseas, Guillermo Mendez, Marcela Carballido, Juan Robbio, Daniel Cisterna, Enrique Roca, Antoni Castells, Francesc Balaguer, Sergi Castellvi-Bel, Marina Antelo
Summary: Lynch syndrome is the most prevalent type of hereditary colorectal cancer, characterized by microsatellite instability. Half of the patients with this syndrome carry germline variants in any of the four mismatch repair DNA genes, while the other half, termed Lynch-like syndrome, have unknown causes. Somatic mutations in genes associated with the MMR system may explain the unexplained MSI in some patients.
Article
Clinical Neurology
Demy J. S. Kuipers, Wim Mandemakers, Chin-Song Lu, Simone Olgiati, Guido J. Breedveld, Christina Fevga, Vera Tadic, Miryam Carecchio, Bradley Osterman, Lena Sagi-Dain, Yah-Huei Wu-Chou, Chiung C. Chen, Hsiu-Chen Chang, Shey-Lin Wu, Tu-Hsueh Yeh, Yi-Hsin Weng, Antonio E. Elia, Celeste Panteghini, Nicolas Marotta, Martje G. Pauly, Andrea A. Kuehn, Jens Volkmann, Baiba Lace, Inge A. Meijer, Krishna Kandaswamy, Marialuisa Quadri, Barbara Garavaglia, Katja Lohmann, Peter Bauer, Niccolo E. Mencacci, Steven J. Lubbe, Christine Klein, Aida M. Bertoli-Avella, Vincenzo Bonifati
Summary: This study identified variants in the EIF2AK2 gene associated with early onset generalized dystonia, which can be dominantly or recessively inherited, or occur de novo. These findings provide direct evidence for the key role of a dysfunctional eIF2 alpha pathway in the pathogenesis of dystonia.
ANNALS OF NEUROLOGY
(2021)
Article
Endocrinology & Metabolism
Sanjoy K. Paul, Jonathan E. Shaw, Peter Fenici, Olga Montvida
Summary: This study aimed to explore the risks and mediation effects of developing chronic kidney disease (CKD) and heart failure (HF) in young- and usual-onset type 2 diabetes (T2D) among White Americans (WAs) and African Americans (AAs). The study found that AAs had a higher risk of developing CKD and HF compared to WAs, and CKD had a greater mediation effect on the HF risk difference between ethnicities compared to HF on CKD risk difference.
Review
Medicine, General & Internal
Frank A. Sinicrope
Summary: Early-onset colorectal cancer, which accounts for 10% of cases, is increasing in incidence, particularly in high-income countries. Patients often present with advanced disease in the left colon, and one in six patients has deficient DNA mismatch repair. Screening is recommended to begin at 45 years of age.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Oncology
Kristin Wallace, Georges J. Nahhas, Christine Bookhout, David N. Lewin, Chrystal M. Paulos, Nana Nikolaishvili-Feinberg, Stephanie M. Cohen, Silvia Guglietta, Ali Bakhtiari, E. Ramsay Camp, Elizabeth G. Hill, John A. Baron, Jennifer D. Wu, Alexander V. Alekseyenko
Summary: This study found that in the early stages of carcinogenesis, African Americans (AAs) may have weaker immune response capacity compared to Caucasian Americans (CAs), indicating an immunosuppressive ('cold') tumor environment in AAs. The results also highlight the importance of colonic location of adenoma in influencing these differences; the reduced immune responses in AAs relative to CAs may indicate impaired immune surveillance in early carcinogenesis. Future studies are needed to understand the role of risk factors (such as obesity) in influencing differences in immune responses by race.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Julia Matas, Brendan Kohrn, Jeanne Fredrickson, Kelly Carter, Ming Yu, Ting Wang, Xianyong Gui, Thierry Soussi, Victor Moreno, William M. Grady, Miguel A. Peinado, Rosa Ana Risques
Summary: This study reveals that mutations in common colorectal cancer genes can be detected in the normal colon, highlighting the prevalent somatic evolution in patients with colorectal cancer. Somatic evolution contributes to clonal expansions in the normal colon, especially in individuals with early-onset colorectal cancer.
Article
Oncology
Hiroshi Y. Yamada, Chao Xu, Kenneth L. Jones, Philip H. O'Neill, Madka Venkateshwar, Srikanth Chiliveru, Hyung-Gyoon Kim, Mark Doescher, Katherine T. Morris, Upender Manne, Chinthalapally V. V. Rao
Summary: The majority of cancer samples analyzed in the US are from white people, resulting in biases in racial and ethnic treatment outcomes. Colorectal cancer rates are higher among African Americans in Alabama and American Indians in Oklahoma. Differences in transcriptomic profiles between racial groups may contribute to these disparities. The expression levels of certain genes and pathways differ significantly in CRCs of African Americans and American Indians compared to white individuals. Targeting strategies designed for white CRC patients may be less effective for these racial groups. These findings highlight the need for optimized interventions to address racial disparities in CRC treatment.
NPJ PRECISION ONCOLOGY
(2023)
Article
Oncology
Guobin Liao, Jun Tang, Jianying Bai
Summary: Esophageal squamous cell carcinoma (ESCC) is a highly malignant cancer with poor prognosis, and its development is based on the classical view of cancer development from stem cell origin and multistep progression. Recent advancements in large-scale and single-cell sequencing technologies, along with transgenic lineage tracing in mouse models, have provided a more detailed understanding of the heterogeneity and early clonal evolution of esophageal stem cells and ESCC. This review discusses the potential relationship between esophageal basal-layer stem cells and cells of ESCC origin, as well as the role of NOTCH1 mutants in the early clonal evolution of ESCCs.
Letter
Medicine, General & Internal
Steven Woloshin, Barnett S. Kramer
Summary: This article discusses the role and limitations of graphs, as well as how to avoid being misled by them. It also mentions a recent journal article that featured a graph considered to be misleading.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Oncology
Minh Duc Do, Thinh Huu Nguyen, Khuong Thai Le, Linh Hoang Gia Le, Bac Hoang Nguyen, Kien Trung Le, Thao Phuong Thi Doan, Chuong Quoc Ho, Hoai-Nghia Nguyen, Tuan Diep Tran, Hoang Anh Vu
Summary: This study on 101 Vietnamese patients with young-onset CRC found that the majority of tumors have multiple gene mutations, with TP53 and APC being the most common mutated genes. Multi-gene panel screening can benefit young-onset CRC patients as well as their relatives due to the decreasing cost of genetic testing.
ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Petr Triska, Kristiyana Kaneva, Daria Merkurjev, Noor Sohail, Marni J. Falk, Timothy J. Triche, Jaclyn A. Biegel, Xiaowu Gai
Article
Oncology
Jun Wang, David Van Den Berg, Amie E. Hwang, Daniel Weisenberger, Timothy Triche, Bharat N. Nathwani, David Conti, Kim Siegmund, Thomas M. Mack, Steve Horvath, Wendy Cozen
LEUKEMIA & LYMPHOMA
(2019)
Article
Oncology
Ben Yi Tew, Christophe Legendre, Mark A. Schroeder, Tim Triche, Gerald C. Gooden, Yizhou Huang, Loren Butry, Daniel J. Ma, Kyle Johnson, Rae Anne Martinez, Mariaelena Pierobon, Emanuel F. Petricoin, Joyce O'Shaughnessy, Cindy Osborne, Coya Tapia, David N. Buckley, Jennifer Glen, Mark Bernstein, Jann N. Sarkaria, Steven A. Toms, Bodour Salhia
Meeting Abstract
Hematology
Hamid Bolouri, Benjamin K. Johnson, Rhonda E. Ries, Laura Pardo, Tiffany A. Hylkema, Wanding Zhou, Jenny L. Smith, Amanda R. Leonti, Allison Kaeding, Michael R. Loken, Jason E. Farrar, Soheil Meshinchi, Timothy Junius Triche
Article
Oncology
Jenny L. Smith, Rhonda E. Ries, Tiffany Hylkema, Todd A. Alonzo, Robert B. Gerbing, Marianne T. Santaguida, Lisa Eidenschink Brodersen, Laura Pardo, Carrie L. Cummings, Keith R. Loeb, Quy Le, Suzan Imren, Amanda R. Leonti, Alan S. Gamis, Richard Aplenc, E. Anders Kolb, Jason E. Farrar, Timothy J. Triche, Cu Nguyen, Daoud Meerzaman, Michael R. Loken, Vivian G. Oehler, Hamid Bolouri, Soheil Meshinchi
CLINICAL CANCER RESEARCH
(2020)
Editorial Material
Oncology
Timothy J. Triche
Article
Medicine, Research & Experimental
Maggie H. Chasse, Benjamin K. Johnson, Elissa A. Boguslawski, Katie M. Sorensen, Jessica E. Rosien, Min H. Kang, C. Patrick Reynolds, Lyong Heo, Zachary B. Madaj, Ian Beddows, Gabrielle E. Foxa, Susan M. Kitchen-Goosen, Bart O. Williams, Timothy J. Triche, Patrick J. Grohar
Summary: The study found that rhabdoid tumors are more sensitive to mithramycin and EC8042, with their sensitivity superior to traditional DNA damaging agents and linked to the causative mutation of SMARCB1 deletion in the tumor. Mithramycin can block the activity of SMARCB1-deficient SWI/SNF complex, leading to chromatin remodeling and restoration of cellular differentiation.
EMBO MOLECULAR MEDICINE
(2021)
Article
Genetics & Heredity
Jamie L. Grit, Benjamin K. Johnson, Patrick S. Dischinger, Curt J. Essenburg, Marie Adams, Stacy Campbell, Kai Pollard, Christine A. Pratilas, Tim J. Triche, Carrie R. Graveel, Matthew R. Steensma
Summary: This study confirms that CNFs and PNFs are epigenetically distinct tumors with differences in higher-order chromatin states and specific methylation events altering genes involved in key biological and cellular processes. The findings demonstrate differential RAS/MKK3/p38 signaling between CNFs and PNFs, with CNFs showing pro-inflammatory signaling and chromatin conformational changes, whereas PNFs signaling predominantly through RAS/MEK. Tumor size also correlated with specific CpG methylation events.
EPIGENETICS & CHROMATIN
(2021)
Article
Hematology
Allison J. Kaeding, Sonali P. Barwe, Anilkumar Gopalakrishnapillai, Rhonda E. Ries, Todd A. Alonzo, Robert B. Gerbing, Colin Correnti, Michael R. Loken, Lisa Eidenschink Broderson, Laura Pardo, Quy H. Le, Thao Tang, Amanda R. Leonti, Jenny L. Smith, Cassie K. Chou, Min Xu, Tim Triche, Steven M. Kornblau, E. Anders Kolb, Katherine Tarlock, Soheil Meshinchi
Summary: The study identified mesothelin (MSLN) as highly overexpressed in a significant proportion of acute myeloid leukemia (AML) patients, associated with certain gene rearrangements and expression patterns, and suggested that MSLN may serve as a diagnostic and therapeutic target in AML. Additionally, MSLN-directed therapeutic strategies, including antibody-drug conjugates (ADCs), showed promising cytotoxic effects in MSLN+ AML cells.
Article
Biochemical Research Methods
Benjamin D. Lee, Anthony Gitter, Casey S. Greene, Sebastian Raschka, Finlay Maguire, Alexander J. Titus, Michael D. Kessler, Alexandra J. Lee, Marc G. Chevrette, Paul Allen Stewart, Thiago Britto-Borges, Evan M. Cofer, Kun-Hsing Yu, Juan Jose Carmona, Elana J. Fertig, Alexandr A. Kalinin, Brandon Signal, Benjamin J. Lengerich, Timothy J. Triche Jr, Simina M. Boca
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Benjamin J. Huang, Jenny L. Smith, Jason E. Farrar, Yi-Cheng Wang, Masayuki Umeda, Rhonda E. Ries, Amanda R. Leonti, Erin Crowgey, Scott N. Furlan, Katherine Tarlock, Marcos Armendariz, Yanling Liu, Timothy Shaw, Lisa Wei, Robert B. Gerbing, Todd M. Cooper, Alan S. Gamis, Richard Aplenc, E. Anders Kolb, Jeffrey Rubnitz, Jing Ma, Jeffery M. Klco, Xiaotu Ma, Todd A. Alonzo, Timothy Triche, Soheil Meshinchi
Summary: The study established a robust transcriptional risk prediction model for pediatric AML, finding that LSC47 is more predictive than LSC17 and increases the predictive power of conventional risk stratification. Applying biomarkers informed by cytomolecular profiling outperforms a uniform approach.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Oncology
Lauren M. Harmon, Timothy J. Triche Jr
Summary: Genomic monitoring is superior to cytogenetics for clinical assessment of leukemia. A case of pediatric acute lymphoblastic leukemia demonstrates that a lesion underlying lethal end-stage myeloid disease could be detected by whole-genome sequencing years before it manifested cytogenetically.
Article
Biochemical Research Methods
Samantha L. Wilson, Shu Yi Shen, Lauren Harmon, Justin M. Burgener, Tim Triche, Scott Bratman, Daniel D. De Carvalho, Michael M. Hoffman
Summary: This study developed a method called cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq) and designed a set of synthetic spike-in DNA controls for quantitative normalization.
CELL REPORTS METHODS
(2022)
Meeting Abstract
Hematology
Benjamin J. Huang, Jenny L. Smith, Rhonda E. Ries, Amanda R. Leonti, Erin Lynn Crowgey, Scott N. Furlan, Timothy Shaw, Lisa Wei, Yi-Cheng Wang, Robert B. Gerbing, Todd A. Alonzo, Todd M. Cooper, Edward A. Kolb, Xiaotu Ma, Jason E. Farrar, Timothy Junius Triche, Soheil Meshinchi
Meeting Abstract
Hematology
Rhonda E. Ries, Timothy Junius Triche, Jenny L. Smith, Amanda R. Leonti, Todd A. Alonzo, Jason E. Farrar, Xiaolong Chen, Yanling Liu, Timothy Shaw, Benjamin J. Huang, Yi-Cheng Wang, Robert B. Gerbing, Betsy A. Hirsch, Susana C. Raimondi, Alan S. Gamis, Richard Aplenc, Jinghui Zhang, E. Anders Kolb, Xiaotu Ma, Soheil Meshinchi