Real-world performance of integrative clinical genomics in pediatric precision oncology.

IF 5.1 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Laboratory Investigation Pub Date : 2024-10-21 DOI:10.1016/j.labinv.2024.102161
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
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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.

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综合临床基因组学在儿科精准肿瘤学中的实际应用。
尽管儿童癌症患者的生存率有了明显提高,但高风险、复发和难治性癌症的治疗效果仍不尽如人意。此外,生存期的延长往往与密集的多模式治疗导致的长期不良反应有关。要加快儿科肿瘤学的发展,既需要治疗方法的进步,也需要减轻长期细胞毒副作用的策略,可能的方法是针对儿科恶性肿瘤的特定分子驱动因素。在本报告中,我们介绍了对 230 名恶性实体瘤患者("原发群组")和 18 名复发或其他难以治疗的非恶性肿瘤患者("继发群组")进行基因组和转录组综合分析的结果。原发群组的整合工作流程能够鉴定出具有临床意义的单核苷酸变异、小插入/缺失和融合基因,分别在 55% 和 28% 的患者中发现了这些变异。对 38% 的患者提出了分子治疗建议。在次级队列中,89%的病例检测到了已知或潜在的驱动基因改变,其中包括包涵体婴儿数字纤维瘤病患者的疑似新致病基因。此外,47%的研究结果还对后续治疗产生了影响。在两个队列中,有4%的病例改变或完善了原始组织病理学诊断。我们的研究表明,整合先进的基因组学和转录组学分析可有效确定治疗靶点、完善诊断并优化治疗策略,用于治疗具有挑战性的儿童和青少年恶性肿瘤,同时也强调了在临床环境中广泛实施精准肿瘤学的必要性。
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来源期刊
Laboratory Investigation
Laboratory Investigation 医学-病理学
CiteScore
8.30
自引率
0.00%
发文量
125
审稿时长
2 months
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.
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