Genomic Profiling of a Large Set of Diverse Pediatric Cancers Identifies Known and Novel Mutations across Tumor Spectra
2017; American Association for Cancer Research; Volume: 77; Issue: 2 Linguagem: Inglês
10.1158/0008-5472.can-16-1106
ISSN1538-7445
AutoresJuliann Chmielecki, Mark Bailey, Jie He, Julia A. Elvin, Jo‐Anne Vergilio, Shakti Ramkissoon, James Suh, Garrett M. Frampton, James Sun, Samantha Morley, Daniel Spritz, Siraj M. Ali, Laurie M. Gay, Rachel Erlich, Jeffrey S. Ross, Joana Buxhaku, Hilary Davies‐Kershaw, Vinny Faso, Alexis Germain, Blair Glanville, Vincent A. Miller, Philip J. Stephens, Katherine A. Janeway, John M. Maris, Soheil Meshinchi, Trevor J. Pugh, Jack F. Shern, Doron Lipson,
Tópico(s)Cancer therapeutics and mechanisms
ResumoAbstract Pediatric cancers are generally characterized by low mutational burden and few recurrently mutated genes. Recent studies suggest that genomic alterations may help guide treatment decisions and clinical trial selection. Here, we describe genomic profiles from 1,215 pediatric tumors representing sarcomas, extracranial embryonal tumors, brain tumors, hematologic malignancies, carcinomas, and gonadal tumors. Comparable published datasets identified similar frequencies of clinically relevant alterations, validating this dataset as biologically relevant. We identified novel ALK fusions in a neuroblastoma (BEND5–ALK) and an astrocytoma (PPP1CB–ALK), novel BRAF fusions in an astrocytoma (BCAS1–BRAF) and a ganglioglioma (TMEM106B–BRAF), and a novel PAX3–GLI2 fusion in a rhabdomyosarcoma. Previously characterized ALK, NTRK1, and PAX3 fusions were observed in unexpected malignancies, challenging the "disease-specific" alterations paradigm. Finally, we identified recurrent variants of unknown significance in MLL3 and PRSS1 predicted to have functional impact. Data from these 1,215 tumors are publicly available for discovery and validation. Cancer Res; 77(2); 509–19. ©2017 AACR.
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