Major Oncogenic Drivers and Their Clinicopathological Correlations in Sporadic Childhood Papillary Thyroid Carcinoma in Belarus

Tatiana I Rogounovitch; Svetlana V Mankovskaya; Mikhail V Fridman; Tatiana A Leonova; Victor A Kondratovitch; Natalya E Konoplya; Shunichi Yamashita; Norisato Mitsutake; Vladimir A Saenko

doi:10.3390/cancers13133374

Major Oncogenic Drivers and Their Clinicopathological Correlations in Sporadic Childhood Papillary Thyroid Carcinoma in Belarus

Cancers (Basel). 2021 Jul 5;13(13):3374. doi: 10.3390/cancers13133374.

Authors

Affiliations

¹ Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852-8523, Japan.
² Institute of Physiology of the National Academy of Sciences of Belarus, 220072 Minsk, Belarus.
³ Republican Centre for Thyroid Tumors, Department of Pathology, Minsk City Clinical Oncologic Dispensary, 220013 Minsk, Belarus.
⁴ Counseling-Diagnostic Department of Thyroid Diseases, Minsk City Clinical Oncologic Dispensary, 220013 Minsk, Belarus.
⁵ Minsk City Clinical Oncologic Dispensary, 220013 Minsk, Belarus.
⁶ N.N.Alexandrov National Cancer Centre of Belarus, Department of Chemotherapy, 223040 Minsk, Belarus.
⁷ Radiation Medical Science Center, Fukushima Medical University, Fukushima 960-1295, Japan.
⁸ Center for Advanced Radiation Emergency Medicine, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.
⁹ Department of Radiation Molecular Epidemiology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852-8523, Japan.

Abstract

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%) BRAF^V600E, 4 (11.8%) RET/PTC1, 6 (17.6%) RET/PTC3, 2 (5.9%) rare fusion genes, and 6 (17.6%) ETV6ex4/NTRK3. No mutations in codons 12, 13, and 61 of K-, N- and H-RAS, BRAF^K601E, or ETV6ex5/NTRK3 or AKAP9/BRAF were detected. Fusion genes were significantly more frequent than BRAF^V600E (p = 0.002). Clinicopathologically, RET/PTC3 was associated with solid growth pattern and higher tumor aggressiveness, BRAF^V600E and RET/PTC1 with classic papillary morphology and mild clinical phenotype, and ETV6ex4/NTRK3 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.

Keywords: Chernobyl; clinicopathological characteristics; gene rearrangement; mutation; papillary thyroid carcinoma; sporadic childhood thyroid cancer.

Abstract

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