Abstract
Clinically significant genomic alterations were identified in pediatric tumors using molecular tumor profiling.
Major Finding: Clinically significant genomic alterations were identified in pediatric tumors using molecular tumor profiling.
Concept: Most diagnostic variants observed were gene fusions, suggesting the clinical importance of their detection.
Impact: Molecular tumor profiling could provide substantial clinical benefit for pediatric patients with extracranial solid tumors.
Targeted next-generation sequencing tests and molecular tumor profiling (MTP) assays have been approved for use in adult solid malignancies, but application of these techniques to validate biomarkers and identify potential therapies in pediatric solid tumors remains to be fully evaluated. Church, Corson, and colleagues determined the clinical impact of MTP with targeted sequencing panels in 389 pediatric patients with 59 distinct types of extracranial solid tumors, a majority of which were sarcomas. Sequencing was performed on 345 patient tumors, with over half being relapsed or refractory disease and the remaining being newly diagnosed. Within the analytical cohort, 69% of patients had at least one gene variant in which a therapeutically actionable recommendation was made, and, of the 200 patients who were eligible for assessment of matched targeted therapy (MTT) response, 29 actually received MTT. In this cohort, 24% met the criteria to be defined as a responder, with all but one patient in this group receiving targeted therapy against a gene fusion that typically included a gene encoding a signaling protein such as NTRK2, ALK, RET, NOTCH, and BRAF. At least one alteration that could impact prognosis was observed in 16% of patients. Additionally, 61% of patients in the cohort harbored alterations that were diagnostically significant, with a majority of these being structural variants that resulted in fusions specific for rare pediatric cancers. MTP also clarified diagnosis in 5% of patients as well as significantly improved diagnostic yields compared to the traditional approaches of fluorescence in situ hybridization and immunohistochemistry. Overall, this study showed that 86% of assessed patients had at least one variant with diagnostic, prognostic, or therapeutic significance, with a majority of variants detected being gene fusions. These results suggest that MTP approaches that include fusion detection can improve pediatric diagnostic classification and patient responses to MTT and guide future pediatric research efforts.
Note:Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.
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