Whole genome and transcriptome integrated analyses guide clinical care of pediatric poor prognosis cancers

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 chi...

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Bibliographic Details
Published in:Nature communications 2024-05, Vol.15 (1), p.4165-4165, Article 4165
Main Authors: Deyell, Rebecca J., Shen, Yaoqing, Titmuss, Emma, Dixon, Katherine, Williamson, Laura M., Pleasance, Erin, Nelson, Jessica M. T., Abbasi, Sanna, Krzywinski, Martin, Armstrong, Linlea, Bonakdar, Melika, Ch’ng, Carolyn, Chuah, Eric, Dunham, Chris, Fok, Alexandra, Jones, Martin, Lee, Anna F., Ma, Yussanne, Moore, Richard A., Mungall, Andrew J., Mungall, Karen L., Rogers, Paul C., Schrader, Kasmintan A., Virani, Alice, Wee, Kathleen, Young, Sean S., Zhao, Yongjun, Jones, Steven J. M., Laskin, Janessa, Marra, Marco A., Rassekh, Shahrad R.
Format: Article
Language:English
Subjects:
38
45/23
45/91
631/208/199
631/208/68
631/208/69
631/67/2332
Adolescent
Bioinformatics
Cancer
Child
Child, Preschool
Children
Copy number
DNA Copy Number Variations
Female
Gene expression
Gene Expression Profiling - methods
Genetic Predisposition to Disease
Genome, Human - genetics
Genomes
Germ-Line Mutation
Humanities and Social Sciences
Humans
Infant
Male
Malignancy
multidisciplinary
Mutation
Neoplasms - genetics
Neoplasms - therapy
Pediatrics
Prognosis
Science
Science (multidisciplinary)
Therapeutic targets
Transcriptome
Transcriptomes
Whole Genome Sequencing
Young Adult
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Description
Summary: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. Efforts to allow routine whole genome and transcriptome analysis (WGTA) for pediatric cancers in the clinic remain critical. Here, the authors present results of a unified genomics and bioinformatics pipeline for WGTA in paediatric cancers, the Personalized OncoGenomics (POG) program, with a focus on potential therapeutic targets.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-48363-5