| Title | Claps | Level | Year | L/Y |
|---|---|---|---|---|
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RET, NTRK, ALK, BRAF and MET fusions in a large cohort of pediatric papillary thyroid carcinomas.
11 auth. B. Pekova, V. Sykorova, S. Dvorakova, E. Václavíková, J. Moravcova, Rami Katra, ...
BACKGROUND
Pediatric papillary thyroid carcinoma (PTC) is a rare malignancy but with an increasing incidence. Pediatric PTCs have distinct clinical and pathological features and even the molecular profile differs from adult PTCs. Somatic point mutat…
BACKGROUND
Pediatric papillary thyroid carcinoma (PTC) is a rare malignancy but with an increasing incidence. Pediatric PTCs have distinct clinical and pathological features and even the molecular profile differs from adult PTCs. Somatic point mutations in pediatric PTCs have been previously described and studied, but complex information about fusion genes is lacking. The aim of this study was to identify different fusion genes in a large cohort of pediatric PTCs and to correlate them with clinical and pathological data of patients.
METHODS
The cohort consisted of 93 pediatric PTC patients (6-20 years old). DNA and RNA were extracted from fresh frozen tissue samples followed by DNA and RNA targeted next generation sequencing analyses. Fusion gene positive samples were verified by Real-Time PCR.
RESULTS
The genetic cause of pediatric PTCs was revealed in 72/93 (77.4%) cases. In 52/93 (55.9%) pediatric PTC patients a fusion gene was detected. Twenty different types of RET, NTRK3, ALK, NTRK1, BRAF and MET fusions were found, of which five novel TPR/RET, IKBKG/RET, BBIP1/RET, OPTN/BRAF, EML4/MET rearrangements were identified and CUL1/BRAF rearrangement has not been previously described in thyroid cancer. Fusion gene positive PTCs were significantly associated with the mixture of classical and follicular variant of PTC, extrathyroidal extension, higher T classification, lymph node and distant metastases, chronic lymphocytic thyroiditis and frequent occurrence of psammoma bodies than fusion gene negative PTCs. Fusion positive patients also received more doses of radioiodine therapy. The most common fusion genes were the RET fusions followed by NTRK3 fusions that were also compared. RET fusions were associated with more frequent lymph node and distant metastases and psammoma bodies and NTRK3 fusions were associated with the follicular variant of PTC.
CONCLUSIONS
Fusion genes were the most common genetic cause of pediatric PTCs. Fusion gene positive PTCs showed more aggressive behavior than fusion gene negative PTCs. Several novel rearrangements were identified. Fusion genes seem to be a molecular marker number one in pediatric PTC patients.
Published in
Thyroid
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8
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6 | 2020 |
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