MultiDimensional ClinOmics for Precision Therapy of Children and Adolescent Young Adults with Relapsed and Refractory Cancer: A Report from the Center for Cancer Research

作者：Chang, Wendy; Brohl, Andrew S.; Patidar, Rajesh; Sindiri, Sivasish; Shern, Jack F.; Wei, Jun S.; Song, Young K.; Yohe, Marielle E.; Gryder, Berkley; Zhang, Shile; Calzone, Kathleen A.; Shivaprasad, Nityashree; Wen, Xinyu; Badgett, Thomas C.; Miettinen, Markku; Hartman, Kip R.; League-Pascual, James C.; Trahair, Toby N.; Widemann, Brigitte C.; Merchant, Melinda S.; Kaplan, Rosandra N.; Lin, Jimmy C.; Khan, Javed^*

来源：Clinical Cancer Research, 2016, 22(15): 3810-3820.

DOI：10.1158/1078-0432.CCR-15-2717

• INCIDENTAL FINDINGS
• GERMLINE MUTATIONS
• GENOMIC LANDSCAPE
• EWING SARCOMA
• GENE
• FUSION
• TUMOR
• RHABDOMYOSARCOMA
• NEUROBLASTOMAS
• ASSOCIATION

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.

• 出版日期2016-8-1