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Occurrence of the Cys611Tyr mutation and a novel Arg886Trp substitution in the RET proto-oncogene in multiple endocrine neoplasia type 2 families and sporadic medullary thyroid carcinoma cases originating from the central region of Portugal.
Clin Endocrinol (Oxf). 2006 Jun; 64(6):659-66.CE

Abstract

OBJECTIVE

Medullary thyroid carcinoma (MTC) occurs both sporadically and in the context of autosomal dominantly inherited multiple endocrine neoplasia type 2 (MEN2) syndromes: MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC), which are caused by activating germline mutations in the RET proto-oncogene. The aim of this study was to characterize the RET mutational spectrum in MEN2 families and apparently sporadic MTC (AS-MTC) cases originating from the central region of Portugal.

SUBJECTS AND METHODS

We studied a total of 82 individuals (64 affected and 18 family members), comprising five MEN2 families (four MEN2A and one MEN2B), as well as 53 AS-MTC cases. RET germline mutations were screened using PCR-DNA sequencing, SSCP and RFLP. The haplotypes associated with recurrent mutations were determined by fragment analysis of microsatellite markers, and by RFLP, in the case of intragenic polymorphisms.

RESULTS

Frequency of the Cys611Tyr (TGC-TAC) mutation was significantly increased in this region of Portugal, due to the fact that three apparently unrelated MEN2A/FMTC families, out of the five in which mutations were identified, harboured this specific mutation. Haplotype analysis revealed that a common haplotype was shared between two of these three families. We have also characterized a novel RET mutation, Arg886Trp, located in the tyrosine kinase domain, which was found in an AS-MTC case.

CONCLUSIONS

There are regional specificities in the relative frequency of RET mutations, which are consistent with a cluster-like distribution of specific disease-causing mutations, as a result of the inheritance of a shared haplotype. These data, along with the finding of a novel RET mutation (Arg886Trp), have important implications towards facilitating and improving the molecular diagnosis of hereditary MTC on a regional basis.

Authors+Show Affiliations

Molecular Pathology Laboratory, Regional Centre of Oncology of Coimbra, Portuguese Institute of Oncology, Coimbra, Portugal. upmolecular@croc.min-saude.ptNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16712668

Citation

Prazeres, Hugo João, et al. "Occurrence of the Cys611Tyr Mutation and a Novel Arg886Trp Substitution in the RET Proto-oncogene in Multiple Endocrine Neoplasia Type 2 Families and Sporadic Medullary Thyroid Carcinoma Cases Originating From the Central Region of Portugal." Clinical Endocrinology, vol. 64, no. 6, 2006, pp. 659-66.
Prazeres HJ, Rodrigues F, Figueiredo P, et al. Occurrence of the Cys611Tyr mutation and a novel Arg886Trp substitution in the RET proto-oncogene in multiple endocrine neoplasia type 2 families and sporadic medullary thyroid carcinoma cases originating from the central region of Portugal. Clin Endocrinol (Oxf). 2006;64(6):659-66.
Prazeres, H. J., Rodrigues, F., Figueiredo, P., Naidenov, P., Soares, P., Bugalho, M. J., Lacerda, M., Campos, B., & Martins, T. C. (2006). Occurrence of the Cys611Tyr mutation and a novel Arg886Trp substitution in the RET proto-oncogene in multiple endocrine neoplasia type 2 families and sporadic medullary thyroid carcinoma cases originating from the central region of Portugal. Clinical Endocrinology, 64(6), 659-66.
Prazeres HJ, et al. Occurrence of the Cys611Tyr Mutation and a Novel Arg886Trp Substitution in the RET Proto-oncogene in Multiple Endocrine Neoplasia Type 2 Families and Sporadic Medullary Thyroid Carcinoma Cases Originating From the Central Region of Portugal. Clin Endocrinol (Oxf). 2006;64(6):659-66. PubMed PMID: 16712668.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Occurrence of the Cys611Tyr mutation and a novel Arg886Trp substitution in the RET proto-oncogene in multiple endocrine neoplasia type 2 families and sporadic medullary thyroid carcinoma cases originating from the central region of Portugal. AU - Prazeres,Hugo João, AU - Rodrigues,Fernando, AU - Figueiredo,Paulo, AU - Naidenov,Plamen, AU - Soares,Paula, AU - Bugalho,Maria João, AU - Lacerda,Manuela, AU - Campos,Beatriz, AU - Martins,Teresa C, PY - 2006/5/23/pubmed PY - 2006/9/16/medline PY - 2006/5/23/entrez SP - 659 EP - 66 JF - Clinical endocrinology JO - Clin Endocrinol (Oxf) VL - 64 IS - 6 N2 - OBJECTIVE: Medullary thyroid carcinoma (MTC) occurs both sporadically and in the context of autosomal dominantly inherited multiple endocrine neoplasia type 2 (MEN2) syndromes: MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC), which are caused by activating germline mutations in the RET proto-oncogene. The aim of this study was to characterize the RET mutational spectrum in MEN2 families and apparently sporadic MTC (AS-MTC) cases originating from the central region of Portugal. SUBJECTS AND METHODS: We studied a total of 82 individuals (64 affected and 18 family members), comprising five MEN2 families (four MEN2A and one MEN2B), as well as 53 AS-MTC cases. RET germline mutations were screened using PCR-DNA sequencing, SSCP and RFLP. The haplotypes associated with recurrent mutations were determined by fragment analysis of microsatellite markers, and by RFLP, in the case of intragenic polymorphisms. RESULTS: Frequency of the Cys611Tyr (TGC-TAC) mutation was significantly increased in this region of Portugal, due to the fact that three apparently unrelated MEN2A/FMTC families, out of the five in which mutations were identified, harboured this specific mutation. Haplotype analysis revealed that a common haplotype was shared between two of these three families. We have also characterized a novel RET mutation, Arg886Trp, located in the tyrosine kinase domain, which was found in an AS-MTC case. CONCLUSIONS: There are regional specificities in the relative frequency of RET mutations, which are consistent with a cluster-like distribution of specific disease-causing mutations, as a result of the inheritance of a shared haplotype. These data, along with the finding of a novel RET mutation (Arg886Trp), have important implications towards facilitating and improving the molecular diagnosis of hereditary MTC on a regional basis. SN - 0300-0664 UR - https://www.unboundmedicine.com/medline/citation/16712668/Occurrence_of_the_Cys611Tyr_mutation_and_a_novel_Arg886Trp_substitution_in_the_RET_proto_oncogene_in_multiple_endocrine_neoplasia_type_2_families_and_sporadic_medullary_thyroid_carcinoma_cases_originating_from_the_central_region_of_Portugal_ L2 - https://doi.org/10.1111/j.1365-2265.2006.02524.x DB - PRIME DP - Unbound Medicine ER -