Pheochromocytoma as the first manifestation of MEN2A with RET mutation S891A: report of a case

Hibi, Yatsuka; Ohye, Tamae; Ogawa, Kimio; Shimizu, Yoshimi; Shibata, Masahiro; Kagawa, Chikara; Mizuno, Yutaka; Uchino, Shigehiko; Kosugi, Shinji; Kurahashi, Hiroki; Iwase, Katsumi

doi:10.1007/s00595-013-0826-8

Cited by 4 publications

(2 citation statements)

References 24 publications

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“…Accordingly, though RET -S891A mutation has been associated to isolated FMTC for several years after its first identification in 1997 [ 29 ], a MEN2 clinical spectrum has been more recently reported in around 4% of cases [ 19 ]. Interestingly, a recent case report paper identify bilateral pheochromocytoma as the first manifestation of MEN2A disease in a patient of a family carrying the RET -S891A mutation [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

The modifier role of RET-G691S polymorphism in hereditary medullary thyroid carcinoma: functional characterization and expression/penetrance studies

Colombo

Minna

Rizzetti

et al. 2015

Orphanet J Rare Dis

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BackgroundHereditary medullary thyroid carcinoma (MTC) is caused by germ-line gain of function mutations in the RET proto-oncogene, and a phenotypic variability among carriers of the same mutation has been reported. We recently observed this phenomenon in a large familial MTC (FMTC) family carrying the RET-S891A mutation. Among genetic modifiers affecting RET-driven MTC, a role has been hypothesized for RET-G691S non-synonymous polymorphism, though the issue remains controversial. Aim of this study was to define the in vitro contribution of RET-G691S to the oncogenic potential of the RET-S891A, previously shown to harbour low transforming activity.MethodsThe RET-S891A and RET-G691S/S891A mutants were generated by site-directed mutagenesis, transiently transfected in HEK293T cells and stably expressed in NIH3T3 cells. Their oncogenic potential was defined by assessing the migration ability by wound healing assay and the anchorage-independent growth by soft agar assay in NIH3T3 cells stably expressing either the single or the double mutants. Two RET-S891A families were characterised for the presence of RET-G691S.ResultsThe functional studies demonstrated that RET-G691S/S891A double mutant displays a higher oncogenic potential than RET-S891A single mutant, assessed by focus formation and migration ability. Moreover, among the 25 RET-S891A carriers, a trend towards an earlier age of diagnosis was found in the MTC patients harboring RET-S891A in association with RET-G691S.ConclusionsWe demonstrate that the RET-G691S non-synonymous polymorphism enhances in vitro the oncogenic activity of RET-S891A. Moreover, an effect on the phenotype was observed in the RET-G691S/S891A patients, thus suggesting that the analysis of this polymorphism could contribute to the decision on the more appropriate clinical and follow-up management.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0231-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The modifier role of RET-G691S polymorphism in hereditary medullary thyroid carcinoma: functional characterization and expression/penetrance studies

Colombo

Minna

Rizzetti

et al. 2015

Orphanet J Rare Dis

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“…There could be clinical differences caused by different amino acid substitutions at codon 634, the C634R mutation was associated with a more aggressive MEN 2A phenotype than the C634Y mutation [5]. Others report Pheochromocytoma as a first manifestation MEN2A with RET mutation S891 A [10]. Treatment will be administered differently depending on each neoplasia.…”

Section: Discussionmentioning

confidence: 99%

Multiple Endocrine Neoplasia 2a: Case Report and Review of Literature

Misri¹

2022

Arch Clin Trial & Case Rep.

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Multiple endocrine neoplasia is a hereditary, autosomal dominant disease. It is created predominantly by RET germline mutations and is considered rare, with a frequency of 1 in 30,000 people. In particular, medullary thyroid cancer associated to this pathology presents at a younger age in relation to sporadic cases. Pheochromocytoma is linked to metastatic disease in only 4% of cases and it is a disease which requires high clinical suspicion. The age of presentation when related to multiple endocrine neoplasia is lower than that of the general population, 38 and 47 years of age respectively. RET proto-oncogene mutation on Codon 634 in exon 11 is the most frequent genetic alteration, present in 85% of cases of MEN2A. Its penetrance for pheochromocytoma is 25% at 30 years and 88% at 77. The objective of this article is to present a case of a patient with MEN2A with bilateral pheochromocytoma and medullary thyroid cancer, discovered in a hypertensive man as an incidental finding.

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Novel Gene Variants in a Nationwide Cohort of Patients with Pheochromocytoma and Paraganglioma

Martínez de Lapiscina,

Diego,

Baquero

et al. 2024

IJMS

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Pheochromocytomas (PCCs) and paragangliomas (PGLs), denoted PPGLs, are rare neuroendocrine tumours and are highly heterogeneous. The phenotype–genotype correlation is poor; therefore, additional studies are needed to understand their pathogenesis. We describe the clinical characteristics of 63 patients with PPGLs and perform a genetic study. Genetic screening was performed via a targeted gene panel, and clinical variables were compared among patients with a positive molecular diagnosis and negative ones in both PCC and PGL cohorts. The mean age of patients with PCC was 50.0, and the mean age of those with PGL was 54.0. Disease-causing germline variants were identified in 16 individuals (25.4%), twelve and five patients with PCC and PGL, respectively. Genetically positive patients were younger at diagnosis in both cohorts. Variants in genes associated with either isolated PPGLs or syndromic forms of the disease were detected in a cohort of PPGLs. We have identified novel variants in known genes and set the importance of genetic screening to every patient with PPGLs, with a special focus on the young. A longer follow up of patients with variants in genes associated with syndromic forms is of clinical value.

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Pheochromocytoma as the first manifestation of MEN2A with RET mutation S891A: report of a case

Cited by 4 publications

References 24 publications

The modifier role of RET-G691S polymorphism in hereditary medullary thyroid carcinoma: functional characterization and expression/penetrance studies

The modifier role of RET-G691S polymorphism in hereditary medullary thyroid carcinoma: functional characterization and expression/penetrance studies

Multiple Endocrine Neoplasia 2a: Case Report and Review of Literature

Novel Gene Variants in a Nationwide Cohort of Patients with Pheochromocytoma and Paraganglioma

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