A Brief Review on The Molecular Basis of Medullary Thyroid Carcinoma

Abstract

Approximately 5-10% of all thyroid cancers are medullary thyroid carcinomas (MTC). MTC is mainly sporadic in nature, but 20-30% of cases are hereditary. Genetic testing for hereditary MTC is very important for the patient and his family, but the patients must be receiving appropriate genetic counseling. About 98% of patients with hereditary MTC have germline mutations in exons 10, 11, 13, 14, 15, 16 and intron 16 of the REarrangement during transfection (RET) proto-oncogene, but the etiology of the more frequent sporadic form of MTC (sMTC) is not well understood. Recently, it has been reported that apparently sporadic MTC may involve point mutations in BRAF and RAS genes, with an overall prevalence of almost 10%. Also alteration and abnormal expression of miRNA has been described in MTC. In this review, we attempted to mention some mutations and molecular changes in sporadic and hereditary MTC pathogenesis.

Keywords: Medullary Thyroid Carcinoma; RET Proto-Oncogene; miRNA.

Fig.1

REarrangement during transfection (RET) structure. RET protein composed a cytoplasmic tyrosine kinase domain, a transmembrane domain, and cysteine rich domain.

Fig.2

RET signaling. RET signaling leads to the activation of the RAS/MAPK and the PI3K/Akt pathways. RET; REarranged during transfection, MAPK; Mitogen-activated protein kinase, BRAF; Proto-oncogene B-Raf, MEK; Is a member of the MAPK signaling cascade, ERK; Extracellular signal-regulated kinases, PI3K; Phosphatidylinositol 3′ kinase, AKT; Is an oncogene that encode serine/threonine-protein kinase, and mTOR; Mechanistic target of rapamycin.

Fig.3

MicroRNA genes are transcribed by RNA polymerase II as pri-microRNA that is processed by a protein complex containing the RNase III enzyme, to form pre-microRNA. Pre-microRNA is processed by a second RNase III enzyme (DICER) to form a mature microRNA with approximately 20-22 nucleotides. The mature microRNAs with ribonuclear particles are incorporated to form the RNA induced silencing complex (RISC) which mediates gene silencing.