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Year : 2015  |  Volume : 4  |  Issue : 2  |  Page : 188-198

Molecular analysis of the rearranged during transfection proto-oncogene in Moroccan patients with medullary thyroid carcinoma

1 Department of Biology, Laboratory of Biochemistry-Immunology, Faculty of Science, Mohammed V University, Rabat; Department of Biology, Laboratory of Genetics, Faculty of Science, Ibn Tofaïl University, Kenitra, Morocco
2 Department of Endocrinology, Diabetology and Nutrition, Ibn Sina Hospital, Rabat, Morocco
3 Department of Biology, Laboratory of Biochemistry-Immunology, Faculty of Science, Mohammed V University, Rabat, Morocco
4 Department of Life Sciences, National Center of Energy, Sciences and Nuclear Techniques, Biology and Medical Research, Rabat, Morocco

Correspondence Address:
Latifa Hilal
Department of Biology, Laboratory of Biochemistry Immunology, Faculty of Science, 4 Avenue Ibn Battouta B.P. 1014 RP, Rabat
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Source of Support: This study has been supported in part by a grant (PROTARS P12/20) from the “Centre National de la Recherche Scientifique et Technique,” Ministry of Higher Education and Scientific Research (CNRST, MEFCRS), Morocco. A part of the DNA sequencing was supported by UATRS-CNRST (Unité d’Appui à la Recherche Scientifique-CNRST), Rabat, Morocco and the Faculty of Science, University Mohammed V, Rabat, Morocco. Abdessamad EL ANNAS and Nabila FRITEZ were recipients of Merit Research Scholarship (from 2009 to 2011) (CNRST-MEFCRS, Morocco), Conflict of Interest: None

DOI: 10.4103/2278-0513.148968

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Background: Germline mutations of the proto-oncogene rearranged during transfection (RET) are pathognomonic of hereditary medullary thyroid carcinoma (MTC). In this study, genetic analysis and familial testing of the RET proto-oncogene in Moroccan families with MTC were performed. Patients and Methods: Thirty-one index cases with MTC and 115 of their relatives were included in this study. The entire coding region of RET was investigated by direct sequencing of polymerase chain reaction products. Once a mutation was identified, the target exon was sequenced in available relatives. Results: Seven distinct germline mutations of RET were identified in 45.2% (14/31) of probands. The most prevalent mutations were located at codon 634 (p.C634R/Y/F) and restricted to families with multiple endocrine neoplasia type 2A (MEN2A) (50% of the 14 mutation carriers, 7/14), followed by mutation at codon 918 (p.M918T) in all MEN2B cases (21.4%, 3/14), then by mutations at codons 804 (p.V804L/M) (14.3%, 2/14); and 891 (p.S891A) (14.3%, 2/14) detected in all patients with apparently sporadic MTC. Familial screening detected RET mutations in 19.1% (22/115) of the studied relatives; 36.4% (8/22) were found with MEN2A symptoms, and 63.6% (14/22) were asymptomatic. About 55% (12/22) were subjected to total therapeutic or prophylactic thyroidectomy. Conclusion: This is the first comprehensive genetic screening showing the spectrum of mutations in RET in Moroccan patients with MTC, which showed a predominance of mutations at codon 634. These results further support the necessity of genetic testing in MTC patients to provide early diagnosis and adequate initial treatment of these patients. This will moreover, contribute to the definition of a national policy for the control of this cancer in Morocco.

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