Multi-Dimensional ClinOmics for Precision Therapy of Children and Adolescent Young Adults with Relapsed and Refractory Cancer: A report from the Center for Cancer Research
Menée sur 59 jeunes patients atteints d'un cancer réfractaire ou récidivant (âge compris entre 7 mois et 25 ans), cette étude américaine évalue la faisabilité d'une technique de séquençage à haut débit pour identifier des mutations d'intérêt clinique
Purpose We undertook a multi-dimensional 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 Food and Drug Administration approved drugs.
Results Fifty-nine patients in 20 diagnostic categories were enrolled from 2010 to 2014. Ages ranged from 7-months-old 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.
Clinical Cancer Research , article en libre accès, 2016