RET Proto Oncogene Mutation Detection and Medullary Thyroid Carcinoma Prevention

Yeganeh, Marjan Zarif; Sheikholeslami, Sara; Hedayati, Mehdi

doi:10.7314/apjcp.2015.16.6.2107

Cited by 18 publications

(13 citation statements)

References 93 publications

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“…Approximately 90% of pedigrees with MEN 2A and familial MTC carry missense mutations in the ECR region cysteine conservative residue (codons 609, 611, 618, and 620 in exon 10 and codons 630 and 634 in exon 11) called hot-spot mutations. These mutations change the protein conformation in the extracellular region, which enhances the transforming capacities of RET, activates tyrosine kinase autophosphorylation, induces cell hyperplasia, and results in various endocrine tumors, including MTC [3,5] . However, the 13 types of variants of the RET gene that we detected in this pedigree did not have the above hot-spot mutations; of these, p.D707E in exon 11 and p.F285S and c.854_855CA in exon 4 have not …”

Section: Discussionmentioning

confidence: 99%

“…Exons 11 and 13 are important functional regions of the RET gene [3,10,22,23] . Among the 13 variants in this pedigree, except p.D707E, p.G691S in exon 11, and p.L769L and p.V778I in exon 13 are located in the region that also codes ITK.…”

Section: Color Version Available Onlinementioning

confidence: 99%

“…HMTC is an autosomal dominant genetic disease with 3 subtypes: multiple endocrine neoplasia type 2A (MEN 2A; 55-60%), multiple endocrine neoplasia type 2B (MEN 2B; 5-10%) and familial MTC (35-40%). MEN 2A is generally accompanied by adrenal pheochromocytoma (PHEO) and/or hyperparathyroidism, and the onset age usually ranges from 20 to 30 years [3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

“…About 75% of all MTC are sporadic forms, while 25% are hereditary MTC (HMTC) [1][2][3] . HMTC is an autosomal dominant genetic disease with 3 subtypes: multiple endocrine neoplasia type 2A (MEN 2A; 55-60%), multiple endocrine neoplasia type 2B (MEN 2B; 5-10%) and familial MTC (35-40%).…”

Section: Introductionmentioning

confidence: 99%

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Rare RET Variant p.D707E in a Chinese Pedigree with Hereditary Medullary Thyroid Carcinoma

Zhang

Li²,

Li³

et al. 2016

Pathobiology

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Background: Hereditary medullary thyroid carcinoma (HMTC) is thought to be associated with germline mutations of the RET proto-oncogene. Methods: We detected RET proto-oncogene germline mutations from a pedigree with HMTC in the east of China and investigated the characteristics of these mutations in this pedigree and their correlation with HMTC by direct sequencing of all 21 exons in the RET gene of all 46 subjects. Results and Conclusion: (1) Thirteen types of RET gene variants were detected in this pedigree. Of these, p.F285S in exon 4, c.854_855CA in exon 4, and p.D707E in exon 11 are reported for the first time in our study. (2) Both linkage disequilibrium analysis and logistic regression analysis showed a significant correlation between the p.D707E variant and HMTC (LOD = 3.69, OR = 4.413, p = 0.000167), indicating that this variant is a risk factor for medullary thyroid carcinoma (MTC). (3) The single-nucleotide polymorphisms (SNP) G691S in exon 11 (rs1799939), S904S in exon 15 (rs1800863), and rs2075912 and rs2565200 in the 3′-untranslated region of the RET proto-oncogene are in complete linkage disequilibrium (D' = 1, r² = 1); no correlation of these SNP and MTC was observed in this pedigree. (4) No hot-spot mutation of the RET proto-oncogene was detected in this pedigree. We drew the conclusion that the heterozygous nonsynonymous variant p.D707E in the RET proto-oncogene is rare, but it is a risk factor for hereditary MTC.

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Section: Discussionmentioning

confidence: 99%

Section: Color Version Available Onlinementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rare RET Variant p.D707E in a Chinese Pedigree with Hereditary Medullary Thyroid Carcinoma

Zhang

Li²,

Li³

et al. 2016

Pathobiology

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show abstract

“…The inherited form of MTC is transmitted as an autosomal dominant trait due to a germline mutation of the RET proto-oncogene that encodes a receptor tyrosine kinase (Yeganeh et al, 2015). The disease may manifest clinically as MTC or as part of syndrome involving other multiple endocrine glands (MEN2) (Eng et al, 1996).…”

Section: Ret Point Mutations:-mentioning

confidence: 99%

Molecular Markers and Thyroid Cancer.

Vuttariello¹,

Chiappetta²

2016

IJAR

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PI3K/AKT Pathway and Its Mediators in Thyroid Carcinomas

Nozhat

Hedayati

2015

Mol Diagn Ther

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Thyroid malignancies are the most common endocrine system carcinomas, with four histopathological forms. The phosphoinositide 3-kinase-protein kinase B/AKT (PI3K-PKB/AKT) pathway is one of the most critical molecular signaling pathways implicated in key cellular processes. Its continuous activation by several aberrant receptor tyrosine kinases (RTKs) and genetic mutations in its downstream effectors result in high cell proliferation in a broad number of cancers, including thyroid carcinomas. In this review article, the role of different signaling pathways of PI3K/AKT in thyroid cancers, with the emphasis on the PI3K/AKT/mammalian target of rapamycin (mTOR), PI3K/AKT/forkhead box O (FOXO) and PI3K/AKT/phosphatase and tensin homolog deleted on chromosome ten (PTEN) pathways, and various therapeutic strategies targeting these pathways have been summarized. In most of the in vitro studies, agents inhibiting mTOR in monotherapy or in combination with chemotherapy for thyroid malignancies have been introduced as promising anticancer therapies. FOXOs and PTEN are two outstanding downstream targets of the PI3K/AKT pathway. At the present time, no study has been undertaken to consider thyroid cancer treatment via FOXOs and PTEN targeting. According to the critical role of these proteins in cell cycle arrest, it seems that a treatment strategy based on the combination of FOXOs or PTEN activity induction with PI3K/AKT downstream mediators (e.g., mTOR) inhibition will be beneficial and promising in thyroid cancer treatment.

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RET Proto Oncogene Mutation Detection and Medullary Thyroid Carcinoma Prevention

Abstract: Thyroid cancer is the most common endocrine neoplasia and accounts for 1% of all human cancers. Medullary thyroid carcinoma (MTC) is a rare malignant

Cited by 18 publications

References 93 publications

Rare RET Variant p.D707E in a Chinese Pedigree with Hereditary Medullary Thyroid Carcinoma

Rare RET Variant p.D707E in a Chinese Pedigree with Hereditary Medullary Thyroid Carcinoma

Molecular Markers and Thyroid Cancer.

PI3K/AKT Pathway and Its Mediators in Thyroid Carcinomas

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