Molecular Characterization of Sporadic Pediatric XXXX with the DNA/RNA ThyroSeq v2 Next-Generation Sequencing Assay.

@entity8958 @entity15529 @entity23275 @entity2250 @entity984 @entity5 @entity9604 @entity13820 @entity10722 @entity146 @entity259 @entity8554 @entity8497 @entity817 @entity8498 @entity6864 @entity2750
The aim of this study was to test the hypothesis that our 60-gene DNA/RNA ThyroSeq v2 next-generation sequence (NGS) assay would identify additional genetic markers, including gene fusions in sporadic pediatric differentiated @entity259 (DTC) that had no known molecular alterations. Sporadic pediatric DTCs with informative molecular testing (n = 18) were studied. We previously tested 15 cases by our standard 7-gene ( @entity817 , @entity8497 , @entity8498 , @entity984 , @entity8958 / @entity2750 , @entity8958 / @entity23275 , @entity15529 / @entity6864 ) mutation panel. Three cases were not tested previously. The standard 7-gene panel identified molecular alterations in 9 of 15 @entity5 (60%). Cases analyzed by ThyroSeq v2 NGS included the six previously negative cases by the standard 7-gene panel and three cases not previously tested. The NGS assay revealed new gene fusions in four of six previously negative cases (67%). These gene fusions included @entity9604 / @entity13820 (n = 3) and @entity10722 / @entity2250 (n = 1). A point mutation ( @entity817 - @entity8554 ) was detected in one of three untested cases. While standard testing could identify only molecular alterations in 60% of cases, with the addition of the ThyroSeq v2 NGS, this increased to 87% (n = 13/15). Some cases with chromosomal rearrangements, including @entity9604 / @entity13820 , appear to be associated with an @entity146 histopathologic phenotype, but had no documented history of radiation exposure. Additional work is needed to investigate if pediatric DTCs could benefit from a reclassification based on molecular subtypes, which may better reflect their underlying biologic potential. Our data support the use of broad gene panels for the molecular diagnostics of pediatric thyroid nodules to aid future classification, treatment, and clinical management recommendations.
