| Summary: | Childhood papillary thyroid carcinoma (PTC) diagnosed after the Chernobyl accident in Belarus displayed a high frequency of gene rearrangements and low frequency of point mutations. Since 2001, only sporadic thyroid cancer occurs in children aged up to 14 years but its molecular characteristics have not been reported. Here, we determine the major oncogenic events in PTC from non-exposed Belarusian children and assess their clinicopathological correlations. Among the 34 tumors, 23 (67.6%) harbored one of the mutually exclusive oncogenes: 5 (14.7%) <i>BRAF<sup>V600E</sup></i>, 4 (11.8%) <i>RET/PTC1</i>, 6 (17.6%) <i>RET/PTC3</i>, 2 (5.9%) rare fusion genes, and 6 (17.6%) <i>ETV6ex4/NTRK3</i>. No mutations in codons 12, 13, and 61 of <i>K-</i>, <i>N-</i> and <i>H-RAS</i>, <i>BRAF<sup>K601E</sup></i>, or <i>ETV6ex5/NTRK3</i> or <i>AKAP9/BRAF</i> were detected. Fusion genes were significantly more frequent than <i>BRAF<sup>V600E</sup></i> (<i>p</i> = 0.002). Clinicopathologically, <i>RET/PTC3</i> was associated with solid growth pattern and higher tumor aggressiveness, <i>BRAF<sup>V600E</sup></i> and <i>RET/PTC1</i> with classic papillary morphology and mild clinical phenotype, and <i>ETV6ex4/NTRK3</i> with follicular-patterned PTC and reduced aggressiveness. The spectrum of driver mutations in sporadic childhood PTC in Belarus largely parallels that in Chernobyl PTC, yet the frequencies of some oncogenes may likely differ from those in the early-onset Chernobyl PTC; clinicopathological features correlate with the oncogene type.
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