Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Nature communications, 2024-05, Vol.15 (1), p.4165-4165, Article 4165

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.