title: Genomic Profiling of a Large Set of Diverse Pediatric Cancers Identifies Known and Novel Mutations across Tumor Spectra.
abstract: 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.
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Juliann
authors.initials: J
authors.lastname: Chmielecki
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Mark
authors.initials: M
authors.lastname: Bailey
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Julia
authors.initials: J
authors.lastname: Elvin
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Jo-Anne
authors.initials: JA
authors.lastname: Vergilio
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Shakti
authors.initials: S
authors.lastname: Ramkissoon
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: James
authors.initials: J
authors.lastname: Suh
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Frampton
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: James X
authors.initials: JX
authors.lastname: Sun
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Samantha
authors.initials: S
authors.lastname: Morley
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Daniel
authors.initials: D
authors.lastname: Spritz
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Siraj
authors.initials: S
authors.lastname: Ali
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Laurie
authors.initials: L
authors.lastname: Gay
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Erlich
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.|Albany Medical College, Albany, New York.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Joana
authors.initials: J
authors.lastname: Buxhaku
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Hilary
authors.initials: H
authors.lastname: Davies
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Vinny
authors.initials: V
authors.lastname: Faso
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Alexis
authors.initials: A
authors.lastname: Germain
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Blair
authors.initials: B
authors.lastname: Glanville
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.|Pediatrics, Harvard Medical School, Boston, Massachusetts.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Janeway
authors.affiliation: Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.affiliation: Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Pugh
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jack F
authors.initials: JF
authors.lastname: Shern
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts. dlipson@foundationmedicine.com.
authors.forename: Doron
authors.initials: D
authors.lastname: Lipson
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D059467:Transcriptome