title: MultiDimensional ClinOmics for Precision Therapy of Children and Adolescent Young Adults with Relapsed and Refractory Cancer: A Report from the Center for Cancer Research.
abstract: We undertook a multidimensional clinical genomics study of children and adolescent young adults with relapsed and refractory cancers to determine the feasibility of genome-guided precision therapy.
  
  
  
  Patients with non-central nervous system solid tumors underwent a combination of whole exome sequencing (WES), whole transcriptome sequencing (WTS), and high-density single-nucleotide polymorphism array analysis of the tumor, with WES of matched germline DNA. Clinically actionable alterations were identified as a reportable germline mutation, a diagnosis change, or a somatic event (including a single nucleotide variant, an indel, an amplification, a deletion, or a fusion gene), which could be targeted with drugs in existing clinical trials or with FDA-approved drugs.
  
  
  
  Fifty-nine patients in 20 diagnostic categories were enrolled from 2010 to 2014. Ages ranged from 7 months to 25 years old. Seventy-three percent of the patients had prior chemotherapy, and the tumors from these patients with relapsed or refractory cancers had a higher mutational burden than that reported in the literature. Thirty patients (51% of total) had clinically actionable mutations, of which 24 (41%) had a mutation that was currently targetable in a clinical trial setting, 4 patients (7%) had a change in diagnosis, and 7 patients (12%) had a reportable germline mutation.
  
  
  
  We found a remarkably high number of clinically actionable mutations in 51% of the patients, and 12% with significant germline mutations. We demonstrated the clinical feasibility of next-generation sequencing in a diverse population of relapsed and refractory pediatric solid tumors. Clin Cancer Res; 22(15); 3810-20. ©2016 AACR.
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. Department of Pediatrics, Molecular Genetics, Columbia University Medical Center, New York, New York.
authors.forename: Wendy
authors.initials: W
authors.lastname: Chang
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. Sarcoma Department, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Brohl
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Patidar
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Sivasish
authors.initials: S
authors.lastname: Sindiri
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Jack F
authors.initials: JF
authors.lastname: Shern
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Jun S
authors.initials: JS
authors.lastname: Wei
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Young K
authors.initials: YK
authors.lastname: Song
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Marielle E
authors.initials: ME
authors.lastname: Yohe
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Berkley
authors.initials: B
authors.lastname: Gryder
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Shile
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Calzone
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Nityashree
authors.initials: N
authors.lastname: Shivaprasad
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wen
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. Pediatric Hematology-Oncology, Kentucky Children's Hospital, Lexington, Kentucky.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Badgett
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Markku
authors.initials: M
authors.lastname: Miettinen
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Maryland. Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Kip R
authors.initials: KR
authors.lastname: Hartman
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. Walter Reed National Military Medical Center, Bethesda, Maryland.
authors.forename: James C
authors.initials: JC
authors.lastname: League-Pascual
authors.affiliation: Centre for Children's Cancer and Blood Disorders, Sydney Children's Hospital, Randwick, New South Wales, Australia.
authors.forename: Toby N
authors.initials: TN
authors.lastname: Trahair
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Brigitte C
authors.initials: BC
authors.lastname: Widemann
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Melinda S
authors.initials: MS
authors.lastname: Merchant
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Rosandra N
authors.initials: RN
authors.lastname: Kaplan
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Jimmy C
authors.initials: JC
authors.lastname: Lin
authors.affiliation: Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. khanjav@mail.nih.gov.
authors.forename: Javed
authors.initials: J
authors.lastname: Khan
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D005260:Female; D023281:Genomics / Q000379:methods; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D008297:Male; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine / Q000379:methods; D012008:Recurrence; D000073359:Exome Sequencing; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor