title: Familial medullary thyroid carcinoma: clinical variability and low aggressiveness associated with RET mutation at codon 804.
abstract: Sixty-one heterozygotes harboring the germline V804L mutation of the RET protooncogene were identified in five independent families. A total of 31 subjects underwent surgery. Histology identified C cell hyperplasia in 30 cases, isolated in 12 and associated with medullary thyroid carcinoma (MTC) in 18. Six patients with MTC had lymph node metastases. Among the 14 patients with basal detectable calcitonin (CT) level, 12 had MTC and 2 had isolated C cell hyperplasia. In most individuals carrying 804 RET mutation, C cell disease displayed late onset and an indolent course; a pentagastrin test was negative in the majority of heterozygotes during the first 2 decades and was positive in only half of them during the third and fourth decades of life. Interestingly, concomitant somatic M918T was detected in a 12-yr-old girl with MTC and was likely to be responsible for both the early clinical appearance and the aggressiveness of the disease. Our data show that in these gene carriers, surgery may be postponed to the fourth decade of life or until the pentagastrin stimulation test becomes positive. Indeed, our data should be confirmed on a larger series of V804L carriers, but may offer a balanced strategy to keep under control and prevent development of the full disease phenotype.
authors.affiliation: Départment de Biologie Clinique and Service de Médecine Nucléaire, Institut Gustave Roussy, Villejuif, France.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lombardo
authors.forename: Eric
authors.initials: E
authors.lastname: Baudin
authors.forename: Eusebio
authors.initials: E
authors.lastname: Chiefari
authors.forename: Franco
authors.initials: F
authors.lastname: Arturi
authors.forename: Stephane
authors.initials: S
authors.lastname: Bardet
authors.forename: Bernard
authors.initials: B
authors.lastname: Caillou
authors.forename: Chiara
authors.initials: C
authors.lastname: Conte
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Dario
authors.initials: D
authors.lastname: Giuffrida
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bidart
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Filetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D018276:Carcinoma, Medullary / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003062:Codon; D029721:Drosophila Proteins; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D003062:Codon; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila