Epigenetics in Medullary Thyroid Cancer: From Pathogenesis to Targeted Therapy.
BACKGROUND
Medullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC. Germline activating mutations of this gene have been reported in about 88-98% of familial MTCs, while somatic mutations of RET gene have been detected in about 23-70% of sporadic forms. Although these genetic events are well characterized, much less is known about the role of epigenetic abnormalities in MTC.


OBJECTIVE
The present review reports a detailed description of epigenetic abnormalities (DNA methylation, histone modifications and miRNA profile), probably involved in the pathogenesis and progression of MTC.


METHODS
A systematic review was performed using Pubmed and Google patents databases.


RESULTS
We report the current understanding of epigenetic patterns in MTC and discuss the potential use of current knowledge in designing novel therapeutic strategies through epigenetic drugs, focusing on recent patents in this field.


CONCLUSIONS
Taking into account the reversibility of epigenetic alterations and the recent development in this field, epigenetic therapy may emerge for clinical use in the near future for patients with advanced MTC.
Istituto Auxologico Italiano, via Zucchi 18, Cusano Milanino, (MI), 20095, Italy. giovanni.vitale@unimi.it.
Giovanni
G
Vitale
Alessandra
A
Dicitore
Erika
E
Messina
Concetta
C
Sciammarella
Antongiulio
A
Faggiano
Annamaria
A
Colao
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015195:Drug Design; D044127:Epigenesis, Genetic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D000090063:Proto-Oncogene Mas; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas