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

• Type: Article in International Scientific Journal
• Date: 2006

Authors

Prazeres, HJ (Author) Other; Rodrigues, F (Author) Other; Figueiredo, P (Author) Other; Naidenov, P (Author) Other; Soares, P (Author) FMUP; Bugalho, MJ (Author) Other; Lacerda, M (Author) Other; Campos, B (Author) Other; Martins, TC (Author) Other

Journal

Title: Clinical Endocrinology

Vol. 64 No. 6

Pages: 659-666

ISSN: 0300-0664

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 19 Citations

ISI Web of Science

Scopus - 20 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

CORDIS: Health sciences

Other information

Authenticus ID: P-004-KB4

DOI: 10.1111/j.1365-2265.2006.02524.x

Abstract (EN): 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 protooncogene. 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8