Deep Sequencing Reveals Occurrence of Subclonal ALK Mutations in Neuroblastoma at Diagnosis.

摘要: Purpose: In neuroblastoma, activating ALK receptor tyrosine kinase point mutations play a major role in oncogenesis. We explored the potential occurrence of at subclonal level using targeted deep sequencing. Experimental Design: clinically representative series 276 diagnostic neuroblastoma samples, exons 23 and 25 gene, containing F1174 R1275 mutation hotspots, respectively, were resequenced with an extremely high depth coverage. Results: At hotspot (exon 23), observed 15 277 samples (range fraction mutated allele per sample: 0.562%–40.409%). 25), detected 12 allele: 0.811%–73.001%). Altogether, events below 20% 15/27 -mutated samples. The presence was associated poorer 5-year overall survival (OS: 75% vs. 57%, P = 0.0212 log-rank test), strong correlation between MYCN amplification being observed. Conclusions: this series, sequencing allows detection mutational diagnosis 10% cases, more than half these, which would have gone undetected by Sanger sequencing. These findings are clinical importance given clonal evolution relapse. also demonstrate techniques for identification patients especially when considering therapy. Clin Cancer Res; 21(21); 4913–21. ©2015 AACR . See related commentary George, [p. 4747][1] [1]: /lookup/volpage/21/4747?iss=21