A 3-platform sequencing approach allowed for identification and characterization of genetic drivers across a wide spectrum of pediatric cancers, according to a study published in Cancer Discovery.

The goal of the Genomes for Kids (G4K) study (ClinicalTrials.gov Identifier: NCT02530658) was to discover more about the novel mechanisms driving a diverse array of pediatric cancers. The 3-platform testing approach encompassed whole-genome, whole-exome, and RNA sequencing.

The researchers sequenced tumor and germline genomes from 309 prospectively identified children with newly diagnosed (85%) or relapsed/refractory (15%) cancers, unselected for tumor type.

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Patients had hematologic malignancies (41%), brain tumors (31%), and non-central nervous system (CNS) solid tumors (27%). Very rare tumor types were present in 15% of patients.

Sequencing results showed that most patients (86%) had at least 1 finding that was diagnostic (53%), prognostic (57%), therapeutically targetable (25%), and/or involved in cancer predisposition (18%).

Sequencing revealed activating gene fusions (36%) that were diagnostic for a cancer type or subgroup. For example, a tumor that was originally classified as a high-grade glioma was found to harbor an MN1-CXCC5 gene fusion, so the tumor was reclassified as a CNS high-grade neuroepithelial tumor with an MN1 alteration.

Sequencing also revealed small intragenic deletions in 15% of tumors and enhancer hijacking translocations in 8%.

The researchers noted that 78 patients in this study presented with or developed metastatic, relapsed, or refractory disease. Sequencing revealed that, in this group, 32 tumors had targetable or potentially targetable lesions or mutation signatures.

Twelve of the 32 patients received targeted treatment based on sequencing results, and 5 of these patients responded to the treatment.

“In summary, the G4K study provides evidence that 3-platform sequencing of tumor and paired normal tissues generates a more detailed picture of the genetic landscape of a tumor, at times revealing clinically relevant information that would go undetected if one used more targeted NGS [next-generation sequencing] approaches,” the study authors wrote.


Newman S, Nakitandwe J, Kesserwan CA, et al. Genomes for kids: The scope of pathogenic mutations in pediatric cancer revealed by comprehensive DNA and RNA sequencing. Cancer Discov. Published online July 23, 2021. doi:10.1158/2159-8290.CD-20-1631