Multiple endocrine neoplasia type 2 syndromes (MEN 2): results from the ItaMEN network analysis on the prevalence of different genotypes and phenotypes

Romei, Cristina; Mariotti, Stefano; Fugazzola, Laura; Taccaliti, Augusto; Pacini, Furio; Opocher, Giuseppe; Mian, Caterina; Castellano, Maurizio; Uberti, Ettore C. degli; Ceccherini, Isabella; Cremonini, Nadia; Seregni, Ettore; Orlandi, Fabio; Ferollà, Piero; Puxeddu, Efisio; Giorgino, Francesco; Colao, Annamaria; Loli, Paola; Bondi, Fabio; Cosci, Barbara; Bottici, Valeria; Cappai, A.; Pinna, G.; Persani, Luca; Verga, Uberta; Boscaro, Marco; Castagna, Maria Grazia; Cappelli, Carlo; Zatelli, Maria Chiara; Faggiano, Antongiulio; Francia, Giuseppe; Brandi, Maria Luisa; Falchetti, Alberto; Pinchera, Aldo; Elisei, Rossella

doi:10.1530/eje-10-0333

Cited by 115 publications

(90 citation statements)

References 43 publications

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“…Our findings are closer to the 57.6% reported in the ItaMEN study (9). It should be noted that in the 'FMTC' group, we have included the cases where pathogenic RET mutation was found even when the family history was negative, because on many occasions the relatives were not available for the study.…”

Section: European Journal Of Endocrinologysupporting

confidence: 82%

“…The exon 11 mutations that are the most frequent in the literature (4,8,9) come in second range in our center with a percentage of 32.8% (19/58). Eleven of these cases carry the Cys634Arg (TGC/CGC) mutation, which is also the commonest in other series.…”

Section: :4mentioning

confidence: 73%

“…The fact that not every RET gene screening program includes exon 8 might be the reason for the rarity of Gly533Cys-positive families outside Western Europe. Two other countries are reported to have a high prevalence of unusual mutations: a large multicenter study form Italy (ItaMEN study) (9) reported that the rare mutation Val804Met in exon 14 is found with a prevalence of 19.6%, especially in Sardinia 59%, followed by the Cys634Arg substitution in exon 11 (13.6%) (9,15). At codons 790/791 in exon 13, another mutations' spot appears with high prevalence in Germany at 13 and 7% respectively (8).…”

Section: :4mentioning

confidence: 99%

“…MEN2 is a rare disease. In recent years, referral centers in several countries have gathered a considerable number of families and published their results which enabled us to correlate RET mutations with the phenotype (8,9).…”

Section: Introductionmentioning

confidence: 99%

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Genetic screening of patients with medullary thyroid cancer in a referral center in Greece during the past two decades

Papathoma

Garofalaki

et al. 2015

European Journal of Endocrinology

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Objective: Mutations in the RET gene are responsible for hereditary medullary thyroid cancer (MTC) and may vary between ethnic groups. We report the spectrum of mutations detected in patients with MTC in a referral center in Greece. Patients and methods: Screening for RET mutations was performed in 313 subjects from 188 unrelated families: 51 patients had clinical suspicion for familial disease, 133 were apparently sporadic, four patients had only C cell hyperplasia, and 125 were family members. Exons 8, 10, 11, and 13-16 were screened. Results: A total of 58 individuals (30.85%) were RET mutations carriers, 120 (63.8%) were finally classified as sporadic, 13 apparently sporadic cases (9.8%) were identified with RET mutation: ten carried the exon 8 at codon 533 mutation (previously reported), two the exon 14 at codon 804 mutation, and one the exon 13 at codon 768 mutation. Six patients (3.19%) with clinical features of multiple endocrine neoplasia type 2A and negative for RET mutations were classified as 'unknown cause'. The mutations of hereditary cases were as follows: 21 cases (36.2%) in exon 8 codon 533, 19 (32.8%) in exon 11 codon 634, nine (15.5%) in exon 10, five (8.6%) in exon 16, three (5.2%) in exon 14 codon 804, and one in exon 13 codon 768 (1.7%). Conclusion:The spectrum of RET mutations in Greece differs from that in other populations and the prevalence of familial cases is higher. The exon 8 (Gly533Cys) mutation was the most prevalent in familial cases unlike other series, followed by exon 11 (codon 634) mutations which are the most frequent elsewhere. The wide application of genetic screening in MTC reveals new molecular defects and helps to characterize the spectrum of mutations in each ethnic group.

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Section: European Journal Of Endocrinologysupporting

confidence: 82%

Section: :4mentioning

confidence: 73%

Section: :4mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Genetic screening of patients with medullary thyroid cancer in a referral center in Greece during the past two decades

Papathoma

Garofalaki

et al. 2015

European Journal of Endocrinology

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“…As a consequence, the information provided for MEN2B is derived from large studies that primarily address MEN2A or from large, poorly described genetic studies with little clinical detail. Three large genetic registries of patients with RET mutations have identified MEN2B in 21/141 (15%, Germany), 20/246 (8.1%, Italy) and 4/145 (2.8%, EUROMEN) patients (Frank-Raue et al 1996, Machens et al 2003, Romei et al 2010, emphasizing the difficulty in collecting robust data about the outcome of patients with MEN2B. Up to now, the largest published descriptive study of MEN2B was based on only 44 patients (Brauckhoff et al 2014).…”

Section: Introductionmentioning

confidence: 99%

A comprehensive review on MEN2B

Castinetti¹,

Moley²,

Mulligan³

et al. 2018

Endocrine-Related Cancer

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MEN2B is a very rare autosomal dominant hereditary tumor syndrome associated with medullary thyroid carcinoma (MTC) in 100% cases, pheochromocytoma in 50% cases and multiple extra-endocrine features, many of which can be quite disabling. Only few data are available in the literature. The aim of this review is to try to give further insights into the natural history of the disease and to point out the missing evidence that would help clinicians optimize the management of such patients. MEN2B is mainly characterized by the early occurrence of MTC, which led the American Thyroid Association to recommend preventive thyroidectomy before the age of 1 year. However, as the majority of mutations are de novo, improved knowledge of the nonendocrine signs would help to lower the age of diagnosis and improve long-term outcomes. Future large-scale studies will be aimed at characterizing more in detail the main characteristics and outcomes of MEN2B.

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Genetic risk association of CDKN1A and RET gene SNPs with medullary thyroid carcinoma: Results from the largest MTC cohort and meta‐analysis

et al. 2019

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Background Medullary thyroid carcinoma (MTC) is a rare subtype of thyroid cancer. Other than gain‐of‐function RET mutations, no other genetic, lifestyle or environmental risk associations have been established for MTC. Several case‐control studies and meta‐analysis have examined the risk association of different SNPs with MTC in different populations but with contradictory or inconclusive results. Methods In a large cohort of 438 Indian MTC cases and 489 gender and ethnicity matched healthy controls from 1000 genome project, a comprehensive risk association of 13 SNPs of three pathways—detoxification, cell cycle regulation and RET was performed along with meta‐analysis of RET SNPs. Results Multivariate logistic regression analysis identified a protective risk association of CDKN1ASer31Arg SNP with both hereditary (OR 0.26; 95% confidence interval [CI] 0.13‐0.55; P < .001) and sporadic MTC (OR 0.53; 95% CI 0.36‐0.78; P = .001). An increased risk association was identified for NAT2Y94Y SNP (OR 1.62, 95% CI 1.17‐2.25, P = .004) and CDKN2A3′UTR SNP (OR 1.89, 95% CI 1.19‐2.98, P = .006) with sporadic MTC and RET S904S with hereditary MTC (OR 2.82, 95% CI 1.64‐4.86, P < .001). Meta‐analysis of RET SNPs including our cohort identified increased risk association of all four RET SNPs with MTC. Conclusion In this largest SNP risk association study for MTC and the only risk association study of the 13 most commonly studied MTC associated SNPs in a single cohort of this rare cancer, a significant protective risk association of CDKN1ASer31Arg SNP with MTC was shown for the first time. Meta‐analysis identified significant risk association of all four RET SNPs, not observed in previous meta‐analysis.

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Multiple endocrine neoplasia type 2 syndromes (MEN 2): results from the ItaMEN network analysis on the prevalence of different genotypes and phenotypes

Cited by 115 publications

References 43 publications

Genetic screening of patients with medullary thyroid cancer in a referral center in Greece during the past two decades

Genetic screening of patients with medullary thyroid cancer in a referral center in Greece during the past two decades

A comprehensive review on MEN2B

Genetic risk association of CDKN1A and RET gene SNPs with medullary thyroid carcinoma: Results from the largest MTC cohort and meta‐analysis

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