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

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 and Shahrad R. Rassekh ()
Additional contact information
Rebecca J. Deyell: BC Children’s Hospital and Research Institute
Yaoqing Shen: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Emma Titmuss: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Katherine Dixon: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Laura M. Williamson: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Erin Pleasance: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Jessica M. T. Nelson: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Sanna Abbasi: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Martin Krzywinski: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Linlea Armstrong: University of British Columbia
Melika Bonakdar: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Carolyn Ch’ng: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Eric Chuah: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Chris Dunham: University of British Columbia
Alexandra Fok: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Martin Jones: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Anna F. Lee: University of British Columbia
Yussanne Ma: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Richard A. Moore: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Andrew J. Mungall: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Karen L. Mungall: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Paul C. Rogers: BC Children’s Hospital and Research Institute
Kasmintan A. Schrader: University of British Columbia
Alice Virani: University of British Columbia
Kathleen Wee: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Sean S. Young: University of British Columbia
Yongjun Zhao: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Steven J. M. Jones: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Janessa Laskin: BC Cancer
Marco A. Marra: Canada’s Michael Smith Genome Sciences Centre at BC Cancer
Shahrad R. Rassekh: BC Children’s Hospital and Research Institute

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-48363-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48363-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-48363-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().