Akademik Veri Yönetim Sistemi
The 62nd Annual ESPE Meeting 2024, Liverpool, İngiltere, 16 - 18 Kasım 2024, ss.75
Background: Our study aimed to determine the molecular characterization of thyroid nodules and cancer in childhood and investigate the
genotype-phenotype relationship.
Methods: The pre-postoperative clinical follow-up features
and genetic characteristics of 62 patients (50 female) were evaluated.
Next-generation sequencing (NGS) was used to investigate common variants in
thyroid lesions with sufficient tissue in the pathology archive. The
patients were divided into three groups based on their pathological diagnoses:
malignant, benign, and other (under follow-up). In
patient samples classified as BC II-VI with sufficient tissue material in the
pathology archive, DNA NGS was used to evaluate variants in 34 genes (AKT1,
ALK, ARID1B, APC, ATM, BRAF, CDKN2A, CDKNB1, DICER1, DNMT3A, EIF1AX, EZH1,
FOXE1, GNAS, HABP2, HRAS, KRAS, LPAR4, MUTYH, NRAS, PIK3CA, POT1, PPM1D, PTEN,
RET, SRRM2, TERT, NKX2-1, TP53, TSHR, ZFHX3, RBM10, MED12, PLEKHS1), and
RNA NGS was used to evaluate variants in RET, ALK, CREB3L2, NTRK1, NTRK2,
NTRK3, BRAF, EML4, PPARG, and IGF2BP3.
Results: The mean age of 62 patients (50F/12M) was 14.2±3.5 (min.:2.7;max.:19
years) with a mean follow-up of 5±3.9
years (min:1.7-max:17.4 years). Of
these, 37 (59.7%) had differentiated
thyroid cancers (DTC), 2 (3.2%) had low-risk tumors, 14 (22.6%) had benign, and 9 (14.5%) had
other cytological findings.
Pathogenic variants were detected in 80% (n=31) of
DTC. The genes with
detected pathological variants, listed in order of frequency, were as follows: BRAF
(n=13), P53 (n=3), NCOA4-RET (n=3), CCDC6-RET (n=3), DICER
(n=2), NRAS (n=2), TSHR (n=1), ALK-STRN (n=1), TPR-NTRK1
(n=1), HRAS (n=1), NTRK3-ETV6 (n=1). BRAFV600E was the most common variant (%37). RET, NTRK, and ALK fusions were
observed in 32%. In the benign group, four had pathogenic variants in DICER,
TSHR, and PTEN.
Among patients in BC, four patients in BC-II (n=14),
six patients in BC-III (n=16), and seven patients in BC-IV (n=10) had DTC. All patients
in BC-V and VI were diagnosed with papillary thyroid cancer(PTC). Pathogenic
variants in DICER (n=1), p53(n=1), and PTEN (n=1) were detected
in patients diagnosed with DTC in BC-II.
According
to the American Thyroid Association Guideline, 28 patients were at low risk,
eight were at moderate risk, and three were at high risk of DTC. Among
high-risk patients, one had NCOA4-RET fusion; two had BRAFV600E.
A 31-year-old patient initially diagnosed with BC-III and had a lobectomy 16 years ago was reevaluated due to the detection of BRAFV600E.
He had no pathological findings in recent control. Among five patients with
persistent disease and PTC diagnosis, four had BRAFV600E. A patient with distant metastasis at diagnosis
had NCOA4-RET. BRAFV600E (n=6), NCOA4-RET (n=3), NTRK3-ETV6
(n=1), and TPR-NTRK1 (n=1) fusions were found in 16 PTC patients with
lymph node involvement.
Conclusion: In this study, BRAFV600E and RET, NTRK, and ALK fusions
were the most common pathogenic variants in children with DTC. BRAFV600E
and NCOA4-RET fusion were seen in patients at high risk. Molecular
studies contribute to patient management in cases initially diagnosed as BC-II-III
with subsequent DTC diagnosis during follow-up.
Keywords: differentiated thyroid cancer, molecular diagnosis
in childhood thyroid cancer, fusion detection with RNA sequencing, DNA and RNA
sequence analysis
*Ankara
University Scientific
Research Committee supported this study.