| Autor: |
Rebecca J. Deyell, Yaoqing Shen, Emma Titmuss, Katherine Dixon, Laura M. Williamson, Erin Pleasance, Jessica M. T. Nelson, Sanna Abbasi, Martin Krzywinski, Linlea Armstrong, Melika Bonakdar, Carolyn Ch’ng, Eric Chuah, Chris Dunham, Alexandra Fok, Martin Jones, Anna F. Lee, Yussanne Ma, Richard A. Moore, Andrew J. Mungall, Karen L. Mungall, Paul C. Rogers, Kasmintan A. Schrader, Alice Virani, Kathleen Wee, Sean S. Young, Yongjun Zhao, Steven J. M. Jones, Janessa Laskin, Marco A. Marra, Shahrad R. Rassekh |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-15 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-48363-5 |
| Popis: |
Abstract The role for routine whole genome and transcriptome analysis (WGTA) for poor prognosis pediatric cancers remains undetermined. Here, we characterize somatic mutations, structural rearrangements, copy number variants, gene expression, immuno-profiles and germline cancer predisposition variants in children and adolescents with relapsed, refractory or poor prognosis malignancies who underwent somatic WGTA and matched germline sequencing. Seventy-nine participants with a median age at enrollment of 8.8 y (range 6 months to 21.2 y) are included. Germline pathogenic/likely pathogenic variants are identified in 12% of participants, of which 60% were not known prior. Therapeutically actionable variants are identified by targeted gene report and whole genome in 32% and 62% of participants, respectively, and increase to 96% after integrating transcriptome analyses. Thirty-two molecularly informed therapies are pursued in 28 participants with 54% achieving a clinical benefit rate; objective response or stable disease ≥6 months. Integrated WGTA identifies therapeutically actionable variants in almost all tumors and are directly translatable to clinical care of children with poor prognosis cancers. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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