Single Point Mutations in Pediatric Differentiated Thyroid Cancer.
Differentiated thyroid cancer (DTC) is rare in children. Previous studies have suggested that it has different clinicopathologic features and mutation profiles compared with adult DTC. However, those studies focused on a single or limited number of gene mutations. This study comprehensively investigated a large series of pediatric DTC for single point mutations in BRAF, HRAS, KRAS, NRAS, PIK3CA, PTEN, and TERT. It also analyzed associations between clinicopathologic features and the BRAFV600Emutation.



Eighty-nine consecutive cases seen in children and adolescents (≤18 years) during 1998-2015 were identified. Rare variants of DTC were excluded, and the study focused on 72 (91.1%) classical papillary thyroid carcinoma (PTC) and seven (8.9%) follicular variant PTC. These included 68 (86.1%) females and 11 (13.9%) males, with a median age of 15.5 years (range 8-18 years). The clinical and histopathological data were obtained from medical records. DNA was extracted from paraffin-embedded tumor tissue, and was PCR-amplified and directly sequenced.



Mutations detected included BRAFV600Ein 19/72 (26.4%) classical PTC samples, and in none of seven follicular variant PTC. Other mutations included: 1/78 (1.3%) successfully amplified tumor samples with TERTC228T; 2/79 (2.5%) NRAS 61 (c.181C>A and c.182A>G); 1/73 (1.4%) PIK3CA exon 9 (c.1589A>G and c.1598C>T in one tumor); 1/79 (1.3%) PIK3CA exon 20 (c.2951G>A); and 1/74 (1.4%) PTEN exon 5 (c.295G>A). No mutation was found in HRAS, KRAS, NRAS12, PTEN exons 6, 7, and 8, and TERTC250T. No significant association was found between BRAFV600Emutation and sex, extrathyroidal invasion, tumor multifocality, vascular invasion, lymph node or distant metastases, and persistent/recurrent disease.



In pediatric DTC, the prevalence of the BRAFV600Emutation is significantly less common compared with adult DTC, and there is no association between this mutation and the histopathological features and outcome of PTC. PIK3CA, PTEN, NRAS 61, and TERTC228Tmutations are rare.
1 Department of Medicine, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia .|2 Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia .
Ali S
AS
Alzahrani
2 Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia .
Avaniyapuram Kannan
AK
Murugan
2 Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia .
Ebtesam
E
Qasem
2 Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia .
Meshael
M
Alswailem
3 Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia .
Hindi
H
Al-Hindi
4 Department of Genetics, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia .
Yufei
Y
Shi
D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D002648:Child; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics; D017354:Point Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012737:Sex Factors; D019098:Telomerase / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
C117307:KRAS protein, human; D008565:Membrane Proteins; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
BRAF; children; mutations; pediatric thyroid cancer; thyroid cancer