RAS proto-oncogene in medullary thyroid carcinoma.
Medullary thyroid carcinoma (MTC) is a rare malignancy originating from the calcitonin-secreting parafollicular thyroid C cells. Approximately 75% of cases are sporadic. Rearranged during transfection (RET) proto-oncogene plays a crucial role in MTC development. Besides RET, other oncogenes commonly involved in the pathogenesis of human cancers have also been investigated in MTC. The family of human RAS genes includes the highly homologous HRAS, KRAS, and NRAS genes that encode three distinct proteins. Activating mutations in specific hotspots of the RAS genes are found in about 30% of all human cancers. In thyroid neoplasias, RAS gene point mutations, mainly in NRAS, are detected in benign and malignant tumors arising from the follicular epithelium. However, recent reports have also described RAS mutations in MTC, namely in HRAS and KRAS. Overall, the prevalence of RAS mutations in sporadic MTC varies between 0-43.3%, occurring usually in tumors with WT RET and rarely in those harboring a RET mutation, suggesting that activation of these proto-oncogenes represents alternative genetic events in sporadic MTC tumorigenesis. Thus, the assessment of RAS mutation status can be useful to define therapeutic strategies in RET WT MTC. MTC patients with RAS mutations have an intermediate risk for aggressive cancer, between those with RET mutations in exons 15 and 16, which are associated with the worst prognosis, and cases with other RET mutations, which have the most indolent course of the disease. Recent results from exome sequencing indicate that, besides mutations in RET, HRAS, and KRAS, no other recurrent driver mutations are present in MTC.
Unidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, PortugalServiço de EndocrinologiaInstituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, PortugalClínica Universitária de EndocrinologiaFaculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo Mártires da Pátria 130, 1150-228 Lisboa, Portugal mmoura@ipolisboa.min-saude.pt.
Margarida M
MM
Moura
Unidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, PortugalServiço de EndocrinologiaInstituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, PortugalClínica Universitária de EndocrinologiaFaculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo Mártires da Pátria 130, 1150-228 Lisboa, Portugal.
Branca M
BM
Cavaco
Unidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, PortugalServiço de EndocrinologiaInstituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, PortugalClínica Universitária de EndocrinologiaFaculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo Mártires da Pátria 130, 1150-228 Lisboa, Portugal Unidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, PortugalServiço de EndocrinologiaInstituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, PortugalClínica Universitária de EndocrinologiaFaculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo Mártires da Pátria 130, 1150-228 Lisboa, Portugal Unidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, PortugalServiço de EndocrinologiaInstituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, PortugalClínica Universitária de EndocrinologiaFaculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo Mártires da Pátria 130, 1150-228 Lisboa, Portugal.
Valeriano
V
Leite
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018276:Carcinoma, Medullary / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018631:ras Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*
D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D018631:ras Proteins
RAS proto-oncogene; correlation with clinicopathological features; medullary thyroid carcinoma; somatic RAS mutations; therapies targeting RAS