TY - JOUR
T1 - Multidimensional clinomics for precision therapy of children and adolescent young adults with relapsed and refractory cancer
T2 - A report from the center for cancer research
AU - Chang, Wendy
AU - Brohl, Andrew S.
AU - Patidar, Rajesh
AU - Sindiri, Sivasish
AU - Shern, Jack F.
AU - Wei, Jun S.
AU - Song, Young K.
AU - Yohe, Marielle E.
AU - Gryder, Berkley
AU - Zhang, Shile
AU - Calzone, Kathleen A.
AU - Shivaprasad, Nityashree
AU - Wen, Xinyu
AU - Badgett, Thomas C.
AU - Miettinen, Markku
AU - Hartman, Kip R.
AU - League-Pascual, James C.
AU - Trahair, Toby N.
AU - Widemann, Brigitte C.
AU - Merchant, Melinda S.
AU - Kaplan, Rosandra N.
AU - Lin, Jimmy C.
AU - Khan, Javed
N1 - Publisher Copyright:
© 2016 AACR.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: 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.
AB - Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: 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.
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U2 - 10.1158/1078-0432.CCR-15-2717
DO - 10.1158/1078-0432.CCR-15-2717
M3 - Article
C2 - 26994145
AN - SCOPUS:84982748005
SN - 1078-0432
VL - 22
SP - 3810
EP - 3820
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 15
ER -