Journal List > Korean J Endocr Surg > v.10(1) > 1059997

M.D., Chi, and M.D.: Genetic Alterations in Follicular Cell-derived Thyroid Carcinomas

Abstract

The molecular approaches to human diseases are receiving greater attention following the completion of the Human Genome Project. Molecular biology techniques are being widely applied to the field of tumor biology, and thyroid carcinomas are not an exception; several genetic alterations have been suggested to play roles in thyroid carcinogenesis and its progression. Malignant tumors arising from thyroid follicular cells can be classified into papillary carcinoma, follicular carcinoma, poorly differentiated carcinoma and anaplastic carcinoma. BRAF mutation, RET/PTC rearrangement and RAS mutation are the suggested molecular causes of papillary thyroid carcinoma (PTC). RAS mutation, PAX8-PPARγrearrangement, PTEN mutation or methylation, and PIK3CA mutation are known to induce follicular thyroid carcinoma (FTC). Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are related to adding p53 or β-catenin gene alterations to those of papillary or follicular carcinomas. The more aggressive genetic alterations are added stepwise as thyroid tumors advance from differentiated PTC or FTC to less differentiated PDTC and finally to ATC. Studying the molecular mechanisms underlying thyroid carcinogenesis may help overcome the limitations of the current diagnostic methods and this may provide more accurate diagnostic and prognostic tools. Furthermore, research at the molecular level is essential for personalized therapies and creating targeted therapies for thyroid carcinomas.

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Fig. 1
Thyroid carcinoma-related signal pathways. Proto-onco-genes and oncogenes are shaded in the diagram. Rectangular figures represent membrane proteins, and round figures cytoplasmic proteins.
kjes-10-1f1.tif
Table 1.
Genetic rearrangements found in papillary thyroid carcinomas
Gene name Oncogene name Fusion gene name Original function of the fusion gene Fusion gene location
RET RET/PTC1 H4 Unknown 10q21
  RET/PTC2 PRKAR1A cAMP-dependent protein kinase regulatory subunit RIalp ha 17q23-24
  RET/PTC3 ELE1 Androgen receptor coactivator 10q11.2
  RET/PTC4 ELE1 Androgen receptor coactivator 10q11.2
  RET/PTC5 RFG5 Golgi autoantigen 14q
  RET/PTC6 HTIF1 Thought to associate with chromatin and heterochromatin-associated factors 7q32-34
  RET/PTC7 RFG7 Thought to be a transcriptional corepressor 1p13
  RET/PTC8 KTN1 Microtubule-associated protein 14q22.1
  RET/PTC8? RFG8 Unknown 18q21-22
NTRK1 TRK TPM3 Tropomyosin family of actin-binding proteins 1q21.2
  TRK/T1 TPR Forms intranuclear filaments attached to the inner surfac of nuclear pore complexes ce 1q25
  TRK/T2 TPR Forms intranuclear filaments attached to the inner surfac of nuclear pore complexes ce 1q25
  TRK/T3 TFG TRK-fused gene 3q12.2
  TRK/T4 TPR Forms intranuclear filaments attached to the inner surfac of nuclear pore complexes ce 1q25
BRAF AKAP9-BR AF AKAP9 PKA binding anchor protein 7q21
Fig. 2
Thyroid carcinoma progression model.
kjes-10-1f2.tif
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