Article
Oncology
Jonas Ecker, Florian Selt, Dominik Sturm, Martin Sill, Andrey Korshunov, Steffen Hirsch, David Capper, Nicola Dikow, Christian Sutter, Carina Mueller, Romain Sigaud, Angelika Eggert, Thorsten Simon, Tim Niehues, Andreas von Deimling, Kristian W. Pajtler, Cornelis M. van Tilburg, David T. W. Jones, Felix Sahm, Stefan M. Pfister, Olaf Witt, Till Milde
Summary: The PTT 2.0 program aims to improve diagnostic accuracy and detect actionable alterations in relapsed pediatric oncology patients, even with limited tumor material. The study utilized molecular analyses such as DNA methylation array, targeted gene panel sequencing, RNA sequencing, and immunohistochemistry to provide relevant and robust information for diagnosis and treatment decisions.
EUROPEAN JOURNAL OF CANCER
(2023)
Review
Pathology
Sheena L. M. Ong, Karoly Szuhai, Judith V. M. G. Bovee
Summary: This review discusses various vascular tumors with recurrent gene fusions, showing the gene fusions and presumed molecular mechanisms underlying tumorigenesis, as well as discussing potential implications for targeted therapies. Identification of gene fusions in vascular tumors has improved diagnostic accuracy over the past decade, providing pathologists with novel diagnostic tools and guiding the development of targeted therapeutic strategies.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2021)
Article
Biotechnology & Applied Microbiology
Stephanie LaHaye, James R. Fitch, Kyle J. Voytovich, Adam C. Herman, Benjamin J. Kelly, Grant E. Lammi, Jeremy A. Arbesfeld, Saranga Wijeratne, Samuel J. Franklin, Kathleen M. Schieffer, Natalie Bir, Sean D. McGrath, Anthony R. Miller, Amy Wetzel, Katherine E. Miller, Tracy A. Bedrosian, Kristen Leraas, Elizabeth A. Varga, Kristy Lee, Ajay Gupta, Bhuvana Setty, Daniel R. Boue, Jeffrey R. Leonard, Jonathan L. Finlay, Mohamed S. Abdelbaki, Diana S. Osorio, Selene C. Koo, Daniel C. Koboldt, Alex H. Wagner, Ann-Kathrin Eisfeld, Krzysztof Mrozek, Vincent Magrini, Catherine E. Cottrell, Elaine R. Mardis, Richard K. Wilson, Peter White
Summary: The EnFusion pipeline utilizes seven fusion calling algorithms to increase the accuracy of identifying clinically relevant fusions in pediatric cancer. By combining ensemble fusion-calling pipeline with a knowledge-based filtering strategy, it accurately identifies driver fusions in pediatric cancer, contributing evidence to diagnosis and guiding targeted therapies where appropriate.
Review
Biochemistry & Molecular Biology
Hanna Goett, Eberhard Uhl
Summary: This review provides an overview of the current research on FGFR3-TACC3 fusions in glioblastoma and discusses their potential implications for clinical practice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Surgery
Stephanie F. Polites, Todd E. Heaton, Michael P. LaQuaglia, Eugene S. Kim, Wesley E. Barry, Catherine J. Goodhue, Andrew J. Murphy, Andrew M. Davidoff, Max R. Langham, Rebecka L. Meyers, Scott S. Short, Timothy B. Lautz, Richard D. Glick, Sanjeev A. Vasudevan, Christina M. Bence, Dave R. Lal, Reto M. Baertschiger, Bryanna Emr, Marcus M. Malek, Roshni Dasgupta
Summary: This study retrospectively analyzed pneumonectomy in 38 children and adolescents with cancer from 1990 to 2017, showing lower rates of postoperative complications and survival rates that were related to tumor type and metastatic status.
Review
Biochemistry & Molecular Biology
Lola Llobat, Olivia Gourbault
Summary: Osteosarcoma is a rare but highly deadly cancer, especially among children and adolescents. The discovery of miRNAs holds potential for earlier diagnosis, prognosis prediction, and development of new therapies for various types of tumors, including OS. The number of clinical trials involving miRNAs as prognostic and diagnostic biomarkers, as well as therapeutic targets, is likely to increase in the near future.
Article
Pathology
Abbas Agaimy, Martina Baneckova, John De Almeida, Brendan C. Dickson, Arno Dimmler, Wolfgang Hartmann, Marick Lae, Jessica Pablik, Christoph Schubart, Alena Skalova, Robert Stoehr, Marcel Trautmann, Eva Wardelmann, Michel Wassef, Ilan Weinreb
Summary: In the past two decades, the nosology of poorly differentiated sinonasal tract malignancies has undergone significant changes, with the discovery of new molecularly defined entities and the identification of genetic driver mutations. A novel sinonasal sarcoma characterized by undifferentiated spindle/round cell morphology and recurrent EWSR1::COLCA2 fusions is described in this study.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2023)
Article
Hematology
Eline J. M. Bertrums, Jenny L. Smith, Lauren Harmon, Rhonda E. Ries, Yi-Cheng J. Wang, Todd A. Alonzo, Andrew J. Menssen, Karen M. Chisholm, Amanda R. Leonti, Katherine Tarlock, Fabiana Ostronoff, Era L. Pogosova-Agadjanyan, Gertjan J. L. Kaspers, Henrik Hasle, Michael Dworzak, Christiane Walter, Nora Muehlegger, Cristina Morerio, Laura Pardo, Betsy Hirsch, Susana Raimondi, Todd M. Cooper, Richard Aplenc, Alan S. Gamis, Edward A. Kolb, Jason E. Farrar, Derek Stirewalt, Xiaotu Ma, Tim I. Shaw, Scott N. Furlan, Lisa Eidenschink Brodersen, Michael R. Loken, Marry M. van den Heuvel-Eibrink, C. Michel Zwaan, Timothy J. Triche, Bianca F. Goemans, Soheil Meshinchi
Summary: NUP98 fusions are rare recurrent alterations in AML, associated with adverse outcomes. Through comprehensive analysis, we found that patients with different fusion partners have distinct characteristics and biology. NUP98-X variants are not cryptic and are associated with WT1 mutations. Fusion partners also define immunophenotypic, transcriptomic, and epigenomic profiles. Importantly, NUP98 fusions predict poor overall survival, except for patients with abnormal chromosome 13.
Review
Biochemistry & Molecular Biology
Megha R. Aepala, Malalage N. Peiris, Zian Jiang, Wei Yang, April N. Meyer, Daniel J. Donoghue
Summary: This article provides a comprehensive compilation of oncogenic fusions involving NTRKs in pediatric soft tissue sarcomas, examining their signaling pathways and activation mechanisms. It also discusses the importance of the N-terminal fusion partner in providing obligatory dimerization or multimerization domains. Therapeutic approaches using different generation agents are presented.
CYTOKINE & GROWTH FACTOR REVIEWS
(2022)
Article
Medicine, General & Internal
Jessica Joseph, Owen Demke, Lola Ameyan, Joseph Bitilinyu-Bango, Blandine Bourgoin, Mamadou Diop, Babacar Gueye, Jibrin Kama, Marvin Lubega, Bernard Madzima, Tatenda Maparo, Tasimba Mhizha, Andrew Musoke, Susan Nabadda, Twambilire Phiri, Timothy Tchereni, Owens Wiwa, Karen Hariharan, Trevor Peter, Shaukat Khan
Summary: This study aimed to demonstrate the acceptability and operational feasibility of introducing HPV testing as a primary cervical cancer screening method in public health programs in sub-Saharan Africa. A total of 15,766 women aged 25-54 years were screened and tested for HPV in 45 primary and secondary health clinics. The results showed that HPV testing was feasible in a public health setting across the five study countries, but there were attrition points in the cascade of care, such as results return and linkage to VIA.
Review
Medicine, General & Internal
Mathias Dzobo, Tafadzwa Dzinamarira, Kabelo Kgarosi, Tivani Phosa Mashamba-Thompson
Summary: This study aims to map the literature on the use of HPVSS for screening cervical cancer in sub-Saharan Africa to identify gaps for future research and practice.
Article
Pathology
Marie-Delphine Lanic, Francois Le Loarer, Vinciane Rainville, Vincent Sater, Mathieu Viennot, Ludivine Beaussire, Pierre-Julien Viailly, Emilie Angot, Isabelle Hostein, Fabrice Jardin, Philippe Ruminy, Marick Lae
Summary: A new molecular diagnostic assay has been developed for the detection of gene fusions in sarcomas. This assay is rapid, reliable, highly sensitive, and multiplexed, facilitating precise diagnosis and identification of tumors with potential targetable fusions.
Review
Oncology
Tracy L. Stockley, Bryan Lo, Adrian Box, Andrea Gomez Corredor, John DeCoteau, Patrice Desmeules, Harriet Feilotter, Daria Grafodatskaya, Cynthia Hawkins, Weei Yuarn Huang, Iyare Izevbaye, Guylaine Lepine, Andreas I. Papadakis, Paul C. Park, Brandon S. Sheffield, Danh Tran-Thanh, Stephen Yip, Ming Sound Tsao
Summary: RNA-based next-generation sequencing (NGS) is an important method in clinical genetic laboratories for detecting gene fusions and guiding targeted therapy selection. A Canadian study highlighted the need for recommendations to optimize gene fusion detection using RNA-based NGS. Consensus recommendations were developed by representatives from 17 Canadian genetic laboratories through working group discussions and surveys, covering pre-analytic, analytic, and reporting aspects of gene fusion detection.
Article
Oncology
Samuele Renzi, Noelle Cullinan, Sarah Cohen-Gogo, Karin Langenberg-Ververgaert, Orli Michaeli, Jalila Alkendi, Nisha Kanwar, Winnie Lo, Anita Villani, Adam Shlien, David Malkin, Anne L. Ryan, Bailey Gallinger, Katrina Ingley, Sevan Hopyan, Abha Gupta, Rose Chami
Summary: This study reported a cohort of very young children with non-rhabdomyosarcoma soft tissue sarcoma, detailing their molecular features, treatment, and outcome. Most common diagnoses included infantile fibrosarcoma, malignant rhabdoid tumor, and undifferentiated sarcoma. Majority of patients underwent tumor molecular characterization and various treatments, with a high survival rate and low disease progression at last follow-up.
PEDIATRIC BLOOD & CANCER
(2021)
Article
Neurosciences
Cheyanne C. Slocum, Hyeon Jin Park, Inji Baek, Jeff Catalano, Martin T. Wells, Benjamin Liechty, Susan Mathew, Wei Song, James P. Solomon, David J. Pisapia
Summary: Since the 2016 WHO Classification, more molecular markers have been found to have prognostic significance in infiltrating gliomas, leading to the incorporation of these markers in the 2021 classification. The Oncomine Cancer Gene Mutation Panel v2 assay has been shown to be superior to immunohistochemistry in detecting IDH1/2 and TP53 mutations and predicting 1p/19q co-deletion. Targeted-next generation sequencing also provides additional information on RNA-based alterations that are diagnostically significant and may have therapeutic implications.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Biology
Karl P. Hodel, Richard de Borja, Erin E. Henninger, Brittany B. Campbell, Nathan Ungerleider, Nicholas Light, Tong Wu, Kimberly G. LeCompte, A. Yasemin Goksenin, Bruce A. Bunnell, Uri Tabori, Adam Shlien, Zachary F. Pursell
Article
Biochemistry & Molecular Biology
Nicholas Light, Veronique Adoue, Bing Ge, Shu-Huang Chen, Tony Kwan, Tomi Pastinen
Article
Biochemistry & Molecular Biology
Veronique Adoue, Alicia Schiavi, Nicholas Light, Jonas Carlsson Almlof, Per Lundmark, Bing Ge, Tony Kwan, Maxime Caron, Lars Ronnblom, Chuan Wang, Shu-Huang Chen, Alison H. Goodall, Francois Cambien, Panos Deloukas, Willem H. Ouwehand, Ann-Christine Syvanen, Tomi Pastinen
MOLECULAR SYSTEMS BIOLOGY
(2014)
Article
Biotechnology & Applied Microbiology
Allison M. Cotton, Bing Ge, Nicholas Light, Veronique Adoue, Tomi Pastinen, Carolyn J. Brown
Article
Oncology
Jun Wang, Diana M. Merino, Nicholas Light, Brian L. Murphy, Yong-Dong Wang, Xiaohui Guo, Andrew P. Hodges, Lianne Q. Chau, Kun-Wei Liu, Girish Dhall, Shahab Asgharzadeh, Erin N. Kiehna, Ryan J. Shirey, Kim D. Janda, Michael D. Taylor, David Malkin, David W. Ellison, Scott R. VandenBerg, Charles G. Eberhart, Rosalie C. Sears, Martine F. Roussel, Richard J. Gilbertson, Robert J. Wechsler-Reya
Article
Oncology
Jiil Chung, Yosef E. Maruvka, Sumedha Sudhaman, Jacalyn Kelly, Nicholas J. Haradhvala, Vanessa Bianchi, Melissa Edwards, Victoria J. Forster, Nuno M. Nunes, Melissa A. Galati, Martin Komosa, Shriya Deshmukh, Vanja Cabric, Scott Davidson, Matthew Zatzman, Nicholas Light, Reid Hayes, Ledia Brunga, Nathaniel D. Anderson, Ben Ho, Karl P. Hodel, Robert Siddaway, A. Sorana Morrissy, Daniel C. Bowers, Valerie Larouche, Annika Bronsema, Michael Osborn, Kristina A. Cole, Enrico Opocher, Gary Mason, Gregory A. Thomas, Ben George, David S. Ziegler, Scott Lindhorst, Magimairajan Vanan, Michal Yalon-Oren, Alyssa T. Reddy, Maura Massimino, Patrick Tomboc, An Van Damme, Alexander Lossos, Carol Durno, Melyssa Aronson, Daniel A. Morgenstern, Eric Bouffet, Annie Huang, Michael D. Taylor, Anita Villani, David Malkin, Cynthia E. Hawkins, Zachary F. Pursell, Adam Shlien, Thomas A. Kunkel, Gad Getz, Uri Tabori
Summary: This study identified a new association between loss of polymerase proofreading and MSI, especially when both components are lost. Analysis of indels in microsatellites revealed five distinct signatures, providing insight into the mechanism of indel formation. The research demonstrates that MS-sigs can be a powerful clinical tool for diagnosing replication repair deficiency and predicting immunotherapy response.
Article
Multidisciplinary Sciences
Nathaniel D. Anderson, Yael Babichev, Fabio Fuligni, Federico Comitani, Mehdi Layeghifard, Rosemarie E. Venier, Stefan C. Dentro, Anant Maheshwari, Sheena Guram, Claire Wunker, J. Drew Thompson, Kyoko E. Yuki, Huayun Hou, Matthew Zatzman, Nicholas Light, Marcus Q. Bernardini, Jay S. Wunder, Irene L. Andrulis, Peter Ferguson, Albiruni R. Abdul Razak, Carol J. Swallow, James J. Dowling, Rima S. Al-Awar, Richard Marcellus, Marjan Rouzbahman, Moritz Gerstung, Daniel Durocher, Ludmil B. Alexandrov, Brendan C. Dickson, Rebecca A. Gladdy, Adam Shlien
Summary: Heterogeneity in leiomyosarcomas (LMS) makes treatment of the disease challenging. Here the authors analyze LMS heterogeneity and molecular LMS subtypes using genomics and transcriptomics, finding origins in distinct lineages and associations with survival, in addition to the early emergence of metastatic clones.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Jung Kim, Nicholas Light, Vallijah Subasri, Erin L. Young, Talia Wegman-Ostrosky, Donald A. Barkauskas, David Hall, Philip J. Lupo, Rajesh Patidar, Luke D. Maese, Kristine Jones, Mingyi Wang, Sean Tavtigian, Dongjing Wu, Adam Shlien, Frank Telfer, Anna Goldenberg, Stephen X. Skapek, Jun S. Wei, Xinyu Wen, Daniel Catchpoole, Douglas S. Hawkins, Joshua D. Schiffman, Javed Khan, David Malkin, Douglas R. Stewart
Summary: In this study, pathogenic germline variants in cancer susceptibility genes were identified in a significant proportion of patients with RMS. These variants did not affect patient survival, but were associated with an earlier age of tumor onset. Additionally, there was a notable excess of pathogenic variants in dominant inheritance genes in certain groups of patients with RMS. Many of these variants had not been previously reported in RMS, indicating the potential for personalized gene-specific therapies and surveillance guidelines for affected individuals.
JCO PRECISION ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Brittany B. Campbell, Nicholas Light, David Fabrizio, Matthew Zatzman, Fabio Fuligni, Richard de Borja, Scott Davidson, Melissa Edwards, Julia A. Elvin, Karl P. Hodel, Walter J. Zahurancik, Zucai Suo, Tatiana Lipman, Katharina Wimmer, Christian P. Kratz, Daniel C. Bowers, Theodore W. Laetsch, Gavin P. Dunn, Tanner M. Johanns, Matthew R. Grimmer, Ivan V. Smirnov, Valerie Larouche, David Samuel, Annika Bronsema, Michael Osborn, Duncan Stearns, Pichai Raman, Kristina A. Cole, Phillip B. Storm, Michal Yalon, Enrico Opocher, Gary Mason, Gregory A. Thomas, Magnus Sabel, Ben George, David S. Ziegler, Scott Lindhorst, Vanan Magimairajan Issai, Shlomi Constantini, Helen Toledano, Ronit Elhasid, Roula Farah, Rina Dvir, Peter Dirks, Annie Huang, Melissa A. Galati, Jiil Chung, Vijay Ramaswamy, Meredith S. Irwin, Melyssa Aronson, Carol Durno, Michael D. Taylor, Gideon Rechavi, John M. Maris, Eric Bouffet, Cynthia Hawkins, Joseph F. Costello, M. Stephen Meyn, Zachary F. Pursell, David Malkin, Uri Tabori, Adam Shlien