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Molecular Characterization of Pediatric Versus Adult Papillary Thyroid Cancers

By: Justine Landin, PhD
Posted: Tuesday, September 28, 2021

The molecular characterization of papillary thyroid tumors appears to be selectively altered across age, according to Young Joo Park, PhD, MD, of Seoul National University, and colleagues. Thus, pediatric patients with papillary thyroid cancer may benefit from genomic profiling, particularly those with progressive, refractory disease. Of note, two pediatric patients with fusion oncogenes and radioactive iodine 131 (I-131)-refractory advanced disease exhibited reduced tumor growth and restoration of radioiodine response following targeted therapy.

“In pediatric fusion-oncogene papillary thyroid cancer cases with I-131–refractory advanced disease, selective fusion-directed therapy may restore radioiodine avidity and lead to a dramatic tumor response, underscoring the importance of molecular testing in pediatric papillary thyroid cancer patients,” stated the study investigators. The findings of this study were published in The Journal of Clinical Investigation.

Tumor samples from pediatric patients (< 20 years old) with papillary thyroid cancer (n = 106) were obtained for genomic profiling and compared with previous transcriptome data from adults with the disease (n = 125). Genomic analysis was conducted using whole-genome sequencing, targeted sequencing, direct sequencing, fluorescence in situ hybridization, and/or immunohistochemistry.

In the pediatric population, genetic drivers were detected in 75% of tumors, fusion oncogenes were seen in 29%, and point mutations were identified in 44%. The most common fusion oncogene was RET, and the most common mutation was BRAF V600E. Fusion oncogenes were most prevalent in tumors of patients younger than age 10 and associated with more advanced and recurrent disease than adolescents with point mutations in BRAF V600E. Further, younger pediatric patients with fusion oncogenes had lower expression of thyroid differentiation genes compared with adults who had fusion-driven papillary thyroid cancer.

Two female pediatric patients with progressive I-131–refractory lung metastases and TRP-NTRK1 or CCDC6-RET fusions were enrolled in a clinical trial to receive fusion-targeted therapy. Larotrectinib and selpercatinib were administered, respectively, and were found to have reduced tumor severity and restored radioiodine uptake in both patients. The patient with the CCDC6-RET fusion also exhibited a tumor response.

Disclosure: The study authors reported no conflicts of interest.



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