Real-World Performance of Integrative Clinical Genomics in Pediatric Precision Oncology
(2024) In Laboratory Investigation 104(12). p.1-12- Abstract
Despite significant improvement in the survival of pediatric patients with cancer, 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... (More)
Despite significant improvement in the survival of pediatric patients with cancer, 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.
(Less)
- author
- publishing date
- 2024-12
- type
- Contribution to journal
- publication status
- published
- keywords
- next-generation sequencing, pediatric oncology, precision medicine
- in
- Laboratory Investigation
- volume
- 104
- issue
- 12
- article number
- 102161
- pages
- 1 - 12
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:39442669
- scopus:85208660409
- ISSN
- 0023-6837
- DOI
- 10.1016/j.labinv.2024.102161
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2024 The Authors
- id
- b060793b-f63d-4c8e-9237-2609ea81a3ec
- date added to LUP
- 2025-02-11 21:23:24
- date last changed
- 2025-07-16 10:03:14
@article{b060793b-f63d-4c8e-9237-2609ea81a3ec,
abstract = {{<p>Despite significant improvement in the survival of pediatric patients with cancer, 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>}},
author = {{Pokorna, Petra and Palova, Hana and Adamcova, Sona and Jugas, Robin and Al Tukmachi, Dagmar and Kyr, Michal and Knoflickova, Dana and Kozelkova, Katerina and Bystry, Vojtech and Mejstrikova, Sona and Merta, Tomas and Trachtova, Karolina and Podlipna, Eliska and Mudry, Peter and Pavelka, Zdenek and Bajciova, Viera and Tinka, Pavel and Jarosova, Marie and Catela Ivkovic, Tina and Madlener, Sibylle and Pal, Karol and Stepien, Natalia and Mayr, Lisa and Tichy, Boris and Drabova, Klara and Jezova, Marta and Kozakova, Sarka and Vanackova, Jitka and Radova, Lenka and Steininger, Karin and Haberler, Christine and Gojo, Johannes and Sterba, Jaroslav and Slaby, Ondrej}},
issn = {{0023-6837}},
keywords = {{next-generation sequencing; pediatric oncology; precision medicine}},
language = {{eng}},
number = {{12}},
pages = {{1--12}},
publisher = {{Nature Publishing Group}},
series = {{Laboratory Investigation}},
title = {{Real-World Performance of Integrative Clinical Genomics in Pediatric Precision Oncology}},
url = {{http://dx.doi.org/10.1016/j.labinv.2024.102161}},
doi = {{10.1016/j.labinv.2024.102161}},
volume = {{104}},
year = {{2024}},
}