Resumen

SANTOS, Marcelo A. C. G. dos et al. Screening of RET gene mutations in multiple endocrine neoplasia type-2 using Conformation Sensitive Gel Electrophoresis (CSGE). Arq Bras Endocrinol Metab [online]. 2007, vol.51, n.9, pp. 1468-1476. ISSN 0004-2730.  http://dx.doi.org/10.1590/S0004-27302007000900009.

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant inherited tumor syndrome caused by RET proto-oncogene germline mutations (RET). Here we tested the Conformation Sensitive Gel Electrophoresis (CSGE) as a screening method for RET hot-spot mutations. Seven MEN2 families were studied by direct sequencing analysis, CSGE and Single Strand Conformational Polymorphism (SSCP). Using CSGE/SSCP, we were able to detect four out of five types of RET mutations verified by sequencing analysis: Cys620Arg, Cys634Arg, Cys634Tyr, and Met918Thr, furthermore a missense substitution at codon 648 (Val648Ile). RET polymorphisms 691 and 769 were also verified. Data obtained using CSGE/SSCP were fully concordant. We conclude that CSGE showed to be a sensitive, fast, low-cost, and simple procedure to detect RET mutations in codons which are reported as the most prevalent RET variants (~ 95%) in large MEN2 series. As to the Val804Met mutation, this method still needs to be optimized.

Palabras llave : Genetic screening; CSGE; SSCP; Genetic sequencing; MEN-2; RET proto-oncogene.