Multiple endocrine neoplasia type 2

Pęczkowska, Mariola; Januszewicz, Andrzej

doi:10.1007/s10689-005-0656-y

Cited by 29 publications

(30 citation statements)

References 112 publications

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“…All of these mutations have been reported previously (Eng 1996, Machens et al 2001, Amar et al 2005. Since other RET mutations have been described in exons 13, 14, and 15 (Peczkowska & Januszewicz 2005), we performed additional SSCP mutation analyses for these exons on the PCC which were negative for mutations in RET exons 10, 11, or 16 or VHL, but no mutations were found. Two patients with bilateral PCC showed the same germline VHL mutation (R64P), and because both patients appeared to be related, they were counted as one patient in our series.…”

Section: Discussionmentioning

confidence: 98%

“…MEN2 is characterized by medullary thyroid carcinoma (MTC) in association with PCC and has three clinical variants, MEN2A, familial medullary thyroid carcinoma (FMTC), and MEN2B (Thakker 2001). The syndrome is caused by germline mutations of the RET proto-oncogene, which are mostly (80-96%) found in RET exons 10, 11, and 16 (Thakker 2001, Peczkowska & Januszewicz 2005. Somatic RET mutations have also been found in sporadic PCC affecting exons 10, 11, and 16 (van der Harst et al 1998b).…”

Section: Introductionmentioning

confidence: 99%

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Candidate gene mutation analysis in bilateral adrenal pheochromocytoma and sympathetic paraganglioma

Korpershoek

Petri²,

Nederveen³

et al. 2007

Endocr Relat Cancer

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Pheochromocytomas (PCCs) are rare tumors that arise from chromaffin tissue in the adrenal medulla, but can also occur in the abdomen outside the adrenals and are then called sympathetic paragangliomas (sPGLs). According to the literature, between 15 and 25% of apparently sporadic adrenal PCC and sPGL are caused by germline mutations in RET, von Hippel-Lindau disease (VHL), succinate dehydrogenase subunit B (SDHB), or subunit D SDHD. However, few studies have addressed the mutation frequency of these candidate genes in selected subgroups of PCC and sPGL, such as bilateral adrenal PCC or extra-adrenal sPGL, and none have looked at somatic mutations by analyzing tumor tissue. Therefore, we have investigated the occurrence of germline and somatic mutations in RET, VHL, SDHB, and SDHD in comparatively large series of bilateral adrenal PCC (nZ 33 patients) and sPGL (nZ26 patients), with the aim of determining the mutation frequency of each of these genes and to establish a genetic testing algorithm. Twenty-one RET, two VHL germline, and one SDHD mutations were found in the patients with bilateral adrenal PCC. In sPGL, one novel SDHB germline and one novel SDHB somatic mutation were observed. In addition, two SDHD germline mutations were found. We conclude that germline RET mutations are predominantly found in bilateral PCC, and that somatic and germline SDHB and SDHD mutations usually occur in sPGL, which has practical consequences for genetic testing algorithms. We suggest that sequential mutation analysis should be directed first at RET, followed by VHL and SDHD for patients with bilateral adrenal PCC at diagnosis, and at SDHB and SDHD for patients with sPGL.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Candidate gene mutation analysis in bilateral adrenal pheochromocytoma and sympathetic paraganglioma

Korpershoek

Petri²,

Nederveen³

et al. 2007

Endocr Relat Cancer

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“…The spectrum of germ line RET mutations in MEN 2 are encompassed by 58 distinct mutations that lie in 19 codons belonging to 7 exons (Peczkowska & Januszewicz 2005;OMIM 164761). It is clear that the MEN 2B-defining mutations, M918T and A883F, portend an aggressive course, with management appropriately aggressive and preemptive (Zbuk & Eng 2007).…”

Section: Introductionmentioning

confidence: 99%

Age-related neoplastic risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germ line RET Cys634Trp (TGC>TGG) mutation

Milos

Frank‐Raue

Wohllk

et al. 2008

Endocrine Related Cancer

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RET testing in multiple endocrine neoplasia type 2 for molecular diagnosis is the paradigm for the practice of clinical cancer genetics. However, precise data for distinct mutation-based risk profiles are not available. Here, we survey the clinical profile for one specific genotype as a model, TGC to TGG in codon 634 (C634W). By international efforts, we ascertained all available carriers of the RET C634W mutation. Age at diagnosis, penetrance, and clinical complications were analyzed for medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism (HPT), as well as overall survival. Our series comprises 92 carriers from 20 unrelated families worldwide. Sixty-eight subjects had MTC diagnosed at age 3-72 years (mean 29). Lymph node metastases were observed in 16 subjects aged 20-72 and distant metastases in 4 subjects aged 28-69. Forty-one subjects had pheochromocytoma detected at age 18-67 (mean 36). Amongst the 28 subjects with MTC and pheochromocytoma, six developed pheochromocytoma before MTC. Six subjects had HPT diagnosed at age 26-52 (mean 39). Eighteen subjects died; of the 16 with known causes of death, 8 died of pheochromocytoma and 4 of MTC. Penetrance for MTC is 52% by age 30 and 83% by age 50, for pheochromocytoma penetrance is 20% by age 30 and 67% by age 50, and for HPT penetrance is 3% by age 30 and 21% by age 50. These data provide, for the first time, RET C634W-specific neoplastic risk and age-related penetrance profiles. The data may facilitate risk assessment and genetic counseling.

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“…MEN2A patients develop medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism. MEN2B, the most distinct and aggressive variant, occurs in ~5% of all cases of MEN2 (2). MEN2B shares the same clinical features as MEN2A except with an earlier onset age, absence of hyperparathyroidism and it has other developmental abnormalities such as decreased upper/ lower body ratio, marfanoid habitus, skeletal deformations, mucosal neuromas, ganglioneuromatosis of the intestinal tract, and myelinated corneal nerves (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

“…The vast majority of MEN2 patients exhibit germ-line mutations in the RET (rearranged during transfection) protooncogene. Up to date, exons 8, 10, 11, 13, 14-16 of RET are hotspots for mutations identified to be associated with MEN2 syndrome in human (2).…”

Section: Introductionmentioning

confidence: 99%

A dog pedigree with familial medullary thyroid cancer

Lee

Lui²,

Höög³

et al. 2006

Int J Oncol

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Abstract. Multiple endocrine neoplasia (MEN) is defined as concurrent neoplasia or hyperplasia in more than one endocrine gland. MEN is well known in humans and has also been reported in small animals. We report on a dog family of a mixed breed with Alaskan malamute as a major influence, where three members developed thyroid carcinomas and another dog had clinical signs mimicking the other three but without a confirmed diagnosis. The age of onset of the tumour was between 96-109 months. Clinical, biochemical and immunohistochemical examinations revealed that the affected individuals typically demonstrated symptoms including calcitonin positive thyroid cancer, hypothyroidism and chronic dermatitis. In addition, elevated serum calcium and multinodular adrenocortical hyperplasia were demonstrated in a single member. The diagnosis observed is similar to the familial form of medullary thyroid carcinoma (FMTC) in human. This is the first report of FMTC in dog. Up to 95% of FMTC and MEN2 is known to be caused by activating mutations in the RET gene. The dog Ret gene was analysed as a candidate in this pedigree. The complete dog Ret genomic sequence was predicted in silico. The lack of demonstratable Ret mutation suggests the involvement of alternative predisposing mutation in this pedigree. The unique occurrence of familial MTC makes this potentially an important model in further defining the genetic basis of MTC.

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Multiple endocrine neoplasia type 2

Cited by 29 publications

References 112 publications

Candidate gene mutation analysis in bilateral adrenal pheochromocytoma and sympathetic paraganglioma

Candidate gene mutation analysis in bilateral adrenal pheochromocytoma and sympathetic paraganglioma

Age-related neoplastic risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germ line RET Cys634Trp (TGC>TGG) mutation

A dog pedigree with familial medullary thyroid cancer

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