Frequency of RET Proto-Oncogene Mutations in Patients with Normal and with Moderately Elevated Pentagastrin-Stimulated Serum Concentrations of Calcitonin

Vierhapper, H.; Bieglmayer, C.; Heinze, Georg; Baumgartner‐Parzer, Sabina

doi:10.1089/1050725041692990

Cited by 35 publications

(19 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our findings are supported by other reports of RET S649L mutations (12,13). In these publications, the MTC-carrying index patients were 44 and 47 years old when first diagnosed.…”

Section: Discussionsupporting

confidence: 92%

Characterization of the RET protooncogene transmembrane domain mutation S649L associated with nonaggressive medullary thyroid carcinoma.

Colombo-Benkmann¹,

Li²,

Riemann³

et al. 2008

European Journal of Endocrinology

View full text Add to dashboard Cite

Context: For rare and novel RET mutations associated with hereditary medullary thyroid carcinoma (MTC), clinical and functional studies are needed to classify the RET mutation into one of the three clinical risk groups. Objective: We analyzed proliferative properties and clinical implications associated with the RET protooncogene transmembrane domain mutation S649L. Design: The transforming potential and mitogenic properties of S649L mutation were investigated clinically and by evaluating kinase activity, cell proliferation, and colony formation. Patients: Fifteen individuals from five kindreds were identified as carriers of a RET protooncogene mutation in exon 11 codon 649 (TCG Ser /TTG Leu ). In two out of five index patients, a second RET mutation (C634W or V804L) was detected. Results: Eight gene carriers were operated on. Histology revealed MTC and C-cell hyperplasia in three index and three screening patients respectively. In all other gene carriers (aged 41-64 years), calcitonin levels were in the normal range, and pentagastrin-stimulated calcitonin levels were !100 pg/ml. Therefore, thyroidectomy had not yet been performed. In one index patient carrying the S649L mutation, hyperparathyroidism was confirmed histologically. RET S649L-expressing NIH3T3 cells exhibited a clear increase of phosphotyrosine and proliferation rate when compared with parental NIH3T3 cells but a significantly lower kinase activity and cell growth rate when compared with RET C634R-expressing cells. When compared with RET C634R, the S649L mutant showed moderate transforming potential with small-sized colonies. Conclusions: Our clinical and in vitro findings indicate that the transmembrane RET S649L mutation is associated with late-onset non-aggressive disease. Recommendations for prophylactic thyroidectomy should be individualized depending on stimulated calcitonin levels.European Journal of Endocrinology 158 811-816

show abstract

“…Our findings are supported by other reports of RET S649L mutations (12,13). In these publications, the MTC-carrying index patients were 44 and 47 years old when first diagnosed.…”

Section: Discussionsupporting

confidence: 92%

Characterization of the RET protooncogene transmembrane domain mutation S649L associated with nonaggressive medullary thyroid carcinoma.

Colombo-Benkmann¹,

Li²,

Riemann³

et al. 2008

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Interestingly, total Tyr791Phe detection rates are nearly similar in our pheochromocytoma and HSCR cohorts (33.3 and 37.5%, respectively). We did not find other additional associated endocrinopathies that had been published previously-such as coexistence of MEN1 syndrome [15], hyperparathyroidism or hyperprolactinemia [16][17][18], and acromegaly [19]. The Tyr791Phe mutation was only observed in a few cases of pheochromocytomas [9,18,[20][21][22].…”

Section: Discussioncontrasting

confidence: 40%

RET mutation Tyr791Phe: the genetic cause of different diseases derived from neural crest

Václavíková

Dvořáková

Sýkorová

et al. 2009

Endocr

View full text Add to dashboard Cite

Activating germline RET mutations are presented in patients with familial medullary thyroid carcinoma (FMTC) and multiple endocrine neoplasia (MEN) types 2A and 2B, whereas inactivating germline mutations in patients with Hirschsprung's disease (HSCR). The aim of this study was to evaluate genotype-phenotype correlations of the frequently discussed Tyr791Phe mutation in exon 13 of the RET proto-oncogene. Screening of three groups of patients was performed (276 families with medullary thyroid carcinoma (MTC), 122 families with HSCR, and 29 patients with pheochromocytoma). We found this mutation in 3 families with apparently sporadic MTC, 3 families with FMTC/MEN2, 1 patient with pheochromocytoma, and 3 families with HSCR. All gene mutation carriers have a silent polymorphism Leu769Leu in exon 13. In three families second germline mutations were detected: Cys620Phe (exon 10) in MEN2A family, Met918Thr (exon 16) in MEN2B family, and Ser649Leu (exon 11) in HSCR patient. Detection of the Tyr791Phe mutation in MEN2/MTC and also in HSCR families leads to the question whether this mutation has a dual character (gain-of-function as well as loss-of-function). A rare case of malignant pheochromocytoma in a patient with the Tyr791Phe mutation is presented. This study shows various clinical characteristics of the frequently discussed Tyr791Phe mutation.

show abstract

“…It is worth noting that the majority of misdiagnosed hereditary cases were FMTC, and their identification was due to systematic RET genetic screening. The relatively low aggressiveness of many of these FMTC forms, especially those caused by noncysteine RET mutations (11,17), may explain the absence of a positive familial history and their clinical diagnosis as sporadic cases. It is also worth noting that all but two of our FMTCs harbor RET mutations in codons other than those typically correlated with the classical MEN 2A and 2B forms, which would not be found if there were not specifically analyzed.…”

Section: Discussionmentioning

confidence: 99%

RETGenetic Screening in Patients with Medullary Thyroid Cancer and Their Relatives: Experience with 807 Individuals at One Center

Elisei

Romei

Cosci

et al. 2007

The Journal of Clinical Endocrinology &Amp; Metabolism

231

124

View full text Add to dashboard Cite

Background: Germline RET gene mutations are causative of multiple endocrine neoplasia (MEN) 2 and may be identified by genetic screening. Three different syndromes are distinguished: MEN 2A, when medullary thyroid carcinoma (MTC) is associated with pheochromocytoma and/or parathyroid adenomas; MEN 2B, when accompanied by a marfanoid habitus and/or pheochromocytoma; and familial medullary thyroid carcinoma (FMTC), when only MTC is present.

show abstract

Frequency of RET Proto-Oncogene Mutations in Patients with Normal and with Moderately Elevated Pentagastrin-Stimulated Serum Concentrations of Calcitonin

Cited by 35 publications

References 12 publications

Characterization of the RET protooncogene transmembrane domain mutation S649L associated with nonaggressive medullary thyroid carcinoma.

Characterization of the RET protooncogene transmembrane domain mutation S649L associated with nonaggressive medullary thyroid carcinoma.

RET mutation Tyr791Phe: the genetic cause of different diseases derived from neural crest

RETGenetic Screening in Patients with Medullary Thyroid Cancer and Their Relatives: Experience with 807 Individuals at One Center

Contact Info

Product

Resources

About