A large family with hereditary MTC: Role of RET genetic analysis in differential diagnosis between MEN 2A and FMTC

E. Chiefari, R. Chiarella, U. Crocetti, B. Tardio, F. Arturi, D. Russo, V. Trischitta, S. Filetti, M. Zingrillo

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Germline mutations of the RET proto-oncogene cause three different cancer syndromes: multiple endocrine neoplasia type 2A (MEN 2A), multiple endocrine neoplasia type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). In the absence of biochemical and/or clinical evidence of pheochromocytoma and hyperparathyroidism, patients with MEN 2A disease display the same phenotype of FMTC disease, although prognosis and clinical management in both affected and unaffected familial members are quite different. We studied a family with hereditary MTC, whose proband was referred to us because of enlarged cervical nodes and increased calcitonin serum levels 28 years after the total thyroidectomy for MTC. Cervical node dissection was carried out and subsequently the presence of MTC metastasis was histologically confirmed. A RET genomic mutation at codon 634 (TGC→TTC) was identified in the proband and in seven out of 19 familial members studied. Accordingly, a hereditary disease was suggested. However, the strong association of RET mutation at codon 634 with the presence of pheochromocytoma in MEN 2 disease suggested a more rigorous management in all gene carriers. Indeed, during the follow-up pheochromocytoma was subsequently identified in the proband. This finding suggests that all families with a pedigree suggestive of FMTC should be regarded at risk from MEN 2A disease, at least when a critical mutation in the RET cysteine domain is detected.

Original languageEnglish
Pages (from-to)52-56
Number of pages5
JournalHormone and Metabolic Research
Volume33
Issue number1
DOIs
Publication statusPublished - 2001

Fingerprint

Multiple Endocrine Neoplasia Type 2a
Pheochromocytoma
Differential Diagnosis
Codon
Mutation
Multiple Endocrine Neoplasia Type 2b
Inborn Genetic Diseases
Proto-Oncogenes
Germ-Line Mutation
Hyperparathyroidism
Thyroid Diseases
Thyroidectomy
Calcitonin
Pedigree
Dissection
Cysteine
Neoplasm Metastasis
Phenotype
Genes
Familial medullary thyroid carcinoma

Keywords

  • Familial Medullary Thyroid Carcinoma (FMTC)
  • Genetic analysis
  • Multiple Endocrine Neoplasia 2A (MEN 2A)
  • Mutation
  • RET proto-oncogene

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Chiefari, E., Chiarella, R., Crocetti, U., Tardio, B., Arturi, F., Russo, D., ... Zingrillo, M. (2001). A large family with hereditary MTC: Role of RET genetic analysis in differential diagnosis between MEN 2A and FMTC. Hormone and Metabolic Research, 33(1), 52-56. https://doi.org/10.1055/s-2001-12627

A large family with hereditary MTC : Role of RET genetic analysis in differential diagnosis between MEN 2A and FMTC. / Chiefari, E.; Chiarella, R.; Crocetti, U.; Tardio, B.; Arturi, F.; Russo, D.; Trischitta, V.; Filetti, S.; Zingrillo, M.

In: Hormone and Metabolic Research, Vol. 33, No. 1, 2001, p. 52-56.

Research output: Contribution to journalArticle

Chiefari, E, Chiarella, R, Crocetti, U, Tardio, B, Arturi, F, Russo, D, Trischitta, V, Filetti, S & Zingrillo, M 2001, 'A large family with hereditary MTC: Role of RET genetic analysis in differential diagnosis between MEN 2A and FMTC', Hormone and Metabolic Research, vol. 33, no. 1, pp. 52-56. https://doi.org/10.1055/s-2001-12627
Chiefari, E. ; Chiarella, R. ; Crocetti, U. ; Tardio, B. ; Arturi, F. ; Russo, D. ; Trischitta, V. ; Filetti, S. ; Zingrillo, M. / A large family with hereditary MTC : Role of RET genetic analysis in differential diagnosis between MEN 2A and FMTC. In: Hormone and Metabolic Research. 2001 ; Vol. 33, No. 1. pp. 52-56.
@article{48302ae76ebc40da80defaf07cccb9cd,
title = "A large family with hereditary MTC: Role of RET genetic analysis in differential diagnosis between MEN 2A and FMTC",
abstract = "Germline mutations of the RET proto-oncogene cause three different cancer syndromes: multiple endocrine neoplasia type 2A (MEN 2A), multiple endocrine neoplasia type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). In the absence of biochemical and/or clinical evidence of pheochromocytoma and hyperparathyroidism, patients with MEN 2A disease display the same phenotype of FMTC disease, although prognosis and clinical management in both affected and unaffected familial members are quite different. We studied a family with hereditary MTC, whose proband was referred to us because of enlarged cervical nodes and increased calcitonin serum levels 28 years after the total thyroidectomy for MTC. Cervical node dissection was carried out and subsequently the presence of MTC metastasis was histologically confirmed. A RET genomic mutation at codon 634 (TGC→TTC) was identified in the proband and in seven out of 19 familial members studied. Accordingly, a hereditary disease was suggested. However, the strong association of RET mutation at codon 634 with the presence of pheochromocytoma in MEN 2 disease suggested a more rigorous management in all gene carriers. Indeed, during the follow-up pheochromocytoma was subsequently identified in the proband. This finding suggests that all families with a pedigree suggestive of FMTC should be regarded at risk from MEN 2A disease, at least when a critical mutation in the RET cysteine domain is detected.",
keywords = "Familial Medullary Thyroid Carcinoma (FMTC), Genetic analysis, Multiple Endocrine Neoplasia 2A (MEN 2A), Mutation, RET proto-oncogene",
author = "E. Chiefari and R. Chiarella and U. Crocetti and B. Tardio and F. Arturi and D. Russo and V. Trischitta and S. Filetti and M. Zingrillo",
year = "2001",
doi = "10.1055/s-2001-12627",
language = "English",
volume = "33",
pages = "52--56",
journal = "Hormone and Metabolic Research",
issn = "0018-5043",
publisher = "Georg Thieme Verlag",
number = "1",

}

TY - JOUR

T1 - A large family with hereditary MTC

T2 - Role of RET genetic analysis in differential diagnosis between MEN 2A and FMTC

AU - Chiefari, E.

AU - Chiarella, R.

AU - Crocetti, U.

AU - Tardio, B.

AU - Arturi, F.

AU - Russo, D.

AU - Trischitta, V.

AU - Filetti, S.

AU - Zingrillo, M.

PY - 2001

Y1 - 2001

N2 - Germline mutations of the RET proto-oncogene cause three different cancer syndromes: multiple endocrine neoplasia type 2A (MEN 2A), multiple endocrine neoplasia type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). In the absence of biochemical and/or clinical evidence of pheochromocytoma and hyperparathyroidism, patients with MEN 2A disease display the same phenotype of FMTC disease, although prognosis and clinical management in both affected and unaffected familial members are quite different. We studied a family with hereditary MTC, whose proband was referred to us because of enlarged cervical nodes and increased calcitonin serum levels 28 years after the total thyroidectomy for MTC. Cervical node dissection was carried out and subsequently the presence of MTC metastasis was histologically confirmed. A RET genomic mutation at codon 634 (TGC→TTC) was identified in the proband and in seven out of 19 familial members studied. Accordingly, a hereditary disease was suggested. However, the strong association of RET mutation at codon 634 with the presence of pheochromocytoma in MEN 2 disease suggested a more rigorous management in all gene carriers. Indeed, during the follow-up pheochromocytoma was subsequently identified in the proband. This finding suggests that all families with a pedigree suggestive of FMTC should be regarded at risk from MEN 2A disease, at least when a critical mutation in the RET cysteine domain is detected.

AB - Germline mutations of the RET proto-oncogene cause three different cancer syndromes: multiple endocrine neoplasia type 2A (MEN 2A), multiple endocrine neoplasia type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). In the absence of biochemical and/or clinical evidence of pheochromocytoma and hyperparathyroidism, patients with MEN 2A disease display the same phenotype of FMTC disease, although prognosis and clinical management in both affected and unaffected familial members are quite different. We studied a family with hereditary MTC, whose proband was referred to us because of enlarged cervical nodes and increased calcitonin serum levels 28 years after the total thyroidectomy for MTC. Cervical node dissection was carried out and subsequently the presence of MTC metastasis was histologically confirmed. A RET genomic mutation at codon 634 (TGC→TTC) was identified in the proband and in seven out of 19 familial members studied. Accordingly, a hereditary disease was suggested. However, the strong association of RET mutation at codon 634 with the presence of pheochromocytoma in MEN 2 disease suggested a more rigorous management in all gene carriers. Indeed, during the follow-up pheochromocytoma was subsequently identified in the proband. This finding suggests that all families with a pedigree suggestive of FMTC should be regarded at risk from MEN 2A disease, at least when a critical mutation in the RET cysteine domain is detected.

KW - Familial Medullary Thyroid Carcinoma (FMTC)

KW - Genetic analysis

KW - Multiple Endocrine Neoplasia 2A (MEN 2A)

KW - Mutation

KW - RET proto-oncogene

UR - http://www.scopus.com/inward/record.url?scp=0035099911&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035099911&partnerID=8YFLogxK

U2 - 10.1055/s-2001-12627

DO - 10.1055/s-2001-12627

M3 - Article

C2 - 11280716

AN - SCOPUS:0035099911

VL - 33

SP - 52

EP - 56

JO - Hormone and Metabolic Research

JF - Hormone and Metabolic Research

SN - 0018-5043

IS - 1

ER -