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- Title
Multigenerational familial medullary thyroid cancer (FMTC): evidence for FMTC phenocopies and association with papillary thyroid cancer.
- Authors
Fugazzola, L; Cerutti, N; Mannavola, D; Ghilardi, G; Alberti, L; Romoli, R; Beck-Peccoz, P
- Abstract
SummarybackgroundOccurrence in a familial setting is well established for medullary thyroid carcinoma (MTC) and has been more recently reported for papillary thyroid cancer (PTC). Germline mutations or rearrangements of the RET proto-oncogene are the genetic background of the majority of hereditary MTCs and of about 25–40% of PTCs. patientsA large multigenerational familial medullary thyroid cancer (FMTC) family, comprised of four generations and a total of 60 subjects, has been fully evaluated. Studies on germline RET mutations and polymorphisms, on somatic RET activation and on haplotyping with RET -linked markers, were performed. resultsRET mutational analysis revealed a rare missense point mutation in exon 15 of RET (A891S), associated with FMTC. Haplotype analysis showed a co-segregation between the allelic variant 5 of D10S578 marker (which is tightly linked to the RET locus) and the RET mutation. Two patients, from different branches of the family, did not harbour the point mutation A891S despite histological confirmation of MTC. In these cases, haplotype analysis excluded the involvement of the RET gene itself in the pathogenesis of the MTC. In three patients, the coexistence, in different foci, of medullary and papillary thyroid cancer was documented. The genetic studies did not show ret /PTC rearrangements. The microsatellite analysis excluded co-segregation of RET locus with the MTC/PTC phenotype. conclusionsWe report a full clinical and molecular analysis of a large FMTC kindred with an uncommon RET mutation. In two family members, phenotype and genotype were not concordant, representing the first evidence of FMTC phenocopies. Furthermore, the association of familial forms of medullary and papillary thyroid cancers has been found in 30% of patients undergoing thyroidectomy for MTC. In these situations, genetic analyses excluded the possible germline involvement of RET . Though FMTC phenocopies are likely to represent an exceptional finding,...
- Subjects
CONUS medullaris; THYROID cancer
- Publication
Clinical Endocrinology, 2002, Vol 56, Issue 1, p53
- ISSN
0300-0664
- Publication type
Article
- DOI
10.1046/j.0300-0664.2001.01434.x