Petra Pokorna, Hana Palova, Sona Adamcova, Robin Jugas, Dagmar Al Tukmachi, Michal Kyr, Dana Knoflickova, Katerina Kozelkova, Vojtech Bystry, Sona Mejstrikova, Tomas Merta, Karolina Trachtova, Eliska Podlipna, Peter Mudry, Zdenek Pavelka, Viera Bajciova, Pavel Tinka, Marie Jarosova, Tina Catela Ivkovic, Sibylle Madlener, Karol Pal, Natalia Stepien, Lisa Mayr, Boris Tichy, Klara Drabova, Marta Jezova, Sarka Kozakova, Jitka Vanackova, Lenka Radova, Karin Steininger, Christine Haberler, Johannes Gojo, Jaroslav Sterba, Ondrej Slaby
{"title":"Real-world performance of integrative clinical genomics in pediatric precision oncology.","authors":"Petra Pokorna, Hana Palova, Sona Adamcova, Robin Jugas, Dagmar Al Tukmachi, Michal Kyr, Dana Knoflickova, Katerina Kozelkova, Vojtech Bystry, Sona Mejstrikova, Tomas Merta, Karolina Trachtova, Eliska Podlipna, Peter Mudry, Zdenek Pavelka, Viera Bajciova, Pavel Tinka, Marie Jarosova, Tina Catela Ivkovic, Sibylle Madlener, Karol Pal, Natalia Stepien, Lisa Mayr, Boris Tichy, Klara Drabova, Marta Jezova, Sarka Kozakova, Jitka Vanackova, Lenka Radova, Karin Steininger, Christine Haberler, Johannes Gojo, Jaroslav Sterba, Ondrej Slaby","doi":"10.1016/j.labinv.2024.102161","DOIUrl":null,"url":null,"abstract":"<p><p>Despite significant improvement in the survival of pediatric cancer patients, treatment outcomes for high-risk, relapsed, and refractory cancers remain unsatisfactory. Moreover, prolonged survival is frequently associated with long-term adverse effects due to intensive multimodal treatments. Accelerating the progress of pediatric oncology requires both therapeutic advances and strategies to mitigate the long-term cytotoxic side effects, potentially through targeting specific molecular drivers of pediatric malignancies. In this report, we present the results of integrative genomic and transcriptomic profiling of 230 patients with malignant solid tumors (the \"primary cohort\") and 18 patients with recurrent or otherwise difficult-to-treat nonmalignant conditions (the \"secondary cohort\"). The integrative workflow for the primary cohort enabled the identification of clinically significant single-nucleotide variants, small insertions/deletions, and fusion genes, which were found in 55% and 28% of patients, respectively. For 38% of patients, molecularly informed treatment recommendations were made. In the secondary cohort, known or potentially driving alteration was detected in 89% of cases, including a suspected novel causal gene for patients with inclusion body infantile digital fibromatosis. Furthermore, 47% of findings also brought therapeutic implications for subsequent management. Across both cohorts, changes or refinements to the original histopathological diagnoses were achieved in 4% of cases. Our study demonstrates the efficacy of integrating advanced genomic and transcriptomic analyses to identify therapeutic targets, refine diagnoses, and optimize treatment strategies for challenging pediatric and young adult malignancies and underscores the need for broad implementation of precision oncology in clinical settings.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Laboratory Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.labinv.2024.102161","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Despite significant improvement in the survival of pediatric cancer patients, treatment outcomes for high-risk, relapsed, and refractory cancers remain unsatisfactory. Moreover, prolonged survival is frequently associated with long-term adverse effects due to intensive multimodal treatments. Accelerating the progress of pediatric oncology requires both therapeutic advances and strategies to mitigate the long-term cytotoxic side effects, potentially through targeting specific molecular drivers of pediatric malignancies. In this report, we present the results of integrative genomic and transcriptomic profiling of 230 patients with malignant solid tumors (the "primary cohort") and 18 patients with recurrent or otherwise difficult-to-treat nonmalignant conditions (the "secondary cohort"). The integrative workflow for the primary cohort enabled the identification of clinically significant single-nucleotide variants, small insertions/deletions, and fusion genes, which were found in 55% and 28% of patients, respectively. For 38% of patients, molecularly informed treatment recommendations were made. In the secondary cohort, known or potentially driving alteration was detected in 89% of cases, including a suspected novel causal gene for patients with inclusion body infantile digital fibromatosis. Furthermore, 47% of findings also brought therapeutic implications for subsequent management. Across both cohorts, changes or refinements to the original histopathological diagnoses were achieved in 4% of cases. Our study demonstrates the efficacy of integrating advanced genomic and transcriptomic analyses to identify therapeutic targets, refine diagnoses, and optimize treatment strategies for challenging pediatric and young adult malignancies and underscores the need for broad implementation of precision oncology in clinical settings.
期刊介绍:
Laboratory Investigation is an international journal owned by the United States and Canadian Academy of Pathology. Laboratory Investigation offers prompt publication of high-quality original research in all biomedical disciplines relating to the understanding of human disease and the application of new methods to the diagnosis of disease. Both human and experimental studies are welcome.