Association of RET codon 691 polymorphism in radiation-induced human thyroid tumours with C-cell hyperplasia in peritumoural tissue

Bounacer, Ali; Villard, Jean; Wicker, R.; Caillou, Bernard; Schlumberger, Martin; Sarasin, Alain; Suárez, H. G.

doi:10.1038/sj.bjc.6600371

Cited by 16 publications

(15 citation statements)

References 49 publications

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“…Significant differences in the frequency of the SNP alleles were not observed in the patient and control groups (table 4), in concordance with several reports (Baumgartner-Parzer et al 2005;Costa et al 2005;Weinhaeusel et al 2008). However, the prevalence of the SNPs in the Indian group was significantly different from the data on European groups including Germans, Italians, French, Spanish and Hungarians (Griseri et al 2000;Bounacer et al 2002;Magalhães et al 2004;Baumgartner-Parzer et al 2005;Costa et al 2005;Bergant et al 2006;Fernandez et al 2006;Guerrero et al 2006;Gursoy et al 2006;Weinhaeusel et al 2008). The SNP in codon 691 has been demonstrated in a collision tumour of the thyroid in an Indian patient (Rekhi et al 2007).…”

Section: Discussionsupporting

confidence: 89%

RET gene mutations and polymorphisms in medullary thyroid carcinomas in Indian patients

Sharma

Saranath

2011

J Biosci

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Germline mutations of RET gene are pathognomonic of multiple endocrine neoplasia (MEN; MEN 2A/MEN 2B) and familial medullary thyroid carcinoma (FMTC), constituting 25% of medullary thyroid carcinomas (MTCs). We investigated RET gene mutations and polymorphisms at exons 10, 11, 13, 14, 15 and 16 in 140 samples, comprising 51 clinically diagnosed MTC patients, 39 family members of patients and 50 normal individuals. The method of choice was PCR and direct nucleotide sequencing of the PCR products. RET gene mutations were detected in 15 (29.4%) patients, with MEN 2A/FMTC in 13 patients and MEN 2B in 2 patients. Further, 39 family members of seven index cases were analysed, wherein four of the seven index cases showed identical mutations, in 13 of 25 family members. We also examined single nucleotide polymorphisms (SNPs) in RET gene exons in 101 unrelated samples. Significant differences in the allelic frequencies of SNPs at codons 691, 769, 836 and 904 between patient and control groups were not observed. However, SNP frequencies were significantly different in the Indian group as compared with other European groups. We identified two novel, rare and unique SNPs separately in single patients. Our study demonstrated presence of MEN 2A/MEN 2B/FMTC-associated mutations in accordance with the reported literature. Thus, RET gene mutations in exons 10, 11, 13, 14, 15 and 16 constitute a rapid test to confirm diagnosis and assess risk of the disease in familial MEN 2A/MEN 2B/FMTC.

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Section: Discussionsupporting

confidence: 89%

RET gene mutations and polymorphisms in medullary thyroid carcinomas in Indian patients

Sharma

Saranath

2011

J Biosci

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“…The G691S RET variant seems to be more frequently expressed in sporadic medullary thyroid carcinomas and in radiation-induced thyroid tumors (36,38). In contrast, the G691S RET polymorphism is underrepresented in patients with Hirschsprung disease (39).…”

Section: Discussionmentioning

confidence: 99%

The G691S RET Polymorphism Increases Glial Cell Line–Derived Neurotrophic Factor–Induced Pancreatic Cancer Cell Invasion by Amplifying Mitogen-Activated Protein Kinase Signaling

Sawai

Okada²,

Kazanjian³

et al. 2005

Cancer Research

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Mutations of the RET proto-oncogene are responsible for several inherited human diseases and may function as genetic modifiers of the disease. However, the role of RET mutations in pancreatic cancer has not been studied. Expression of the glial cell line-derived neurotrophic factor (GDNF) receptors RET and GDNF family receptor A1 (GFRA1) in human pancreatic cancer cells was determined by Western blot, immunofluorescence, and flow cytometry. The effect of GDNF on cell proliferation and invasion was assessed. Small interfering RNA and antibodies were used to evaluate the involvement of RET. The G691S RET polymorphism was analyzed by sequencing and restriction analysis. The modifying effect of G691S RET on GDNF-induced invasion and mitogen-activated protein kinase (MAPK) signaling was evaluated. Transfection studies with wild-type and mutated RET determined the functional role of the G691S polymorphism. Pancreatic cancer specimens and matched tissues were analyzed for the presence of the G691S RET polymorphism. GDNF receptors were found on all cell lines. GDNF increased pancreatic cancer cell proliferation and invasion, which was mediated by RET. The effect of GDNF was more profound in cells with the G691S RET polymorphism (P < 0.01). G691S RET correlated with an enhanced activation of the downstream extracellular signal-regulated kinase pathway. Overexpression of G691S RET increased pancreatic cancer cell invasion. The G691S RET polymorphism was also detected in human pancreatic tumors and represented a somatic mutation in some patients. These findings indicate that the G691S RET single nucleotide polymorphism may directly correlate with the aggressive growth of pancreatic cancers and may function as a genetic modifier or even lowpenetrance gene. (Cancer Res 2005; 65(24): 11536-44)

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“…The incidence of CCH in thyroid tissue adjacent to follicular cell tumors is significant (35-50%) [2,19]. The incidence of peritumoral CCH is further increased in patients with radiation-induced epithelial thyroid tumors than adjacent to sporadic thyroid tumors [28]. An iodine-deficient diet or propylthiouracil administration could be accompanied by an increase in calcitonin levels, suggesting a potential role of thyroid-stimulating hormone (TSH) in C cell regulation [19].…”

Section: Classificationmentioning

confidence: 99%

“…Reactive CCH may result through an immunopathological mechanism or via an effect of the inflammatory mediators and cytokines secreted by the infiltrating inflammatory cells in the thyroid parenchyma [19]. There is evidence suggesting the involvement of a functional interconnection between follicular and parafollicular C cells [28]. A thyroid pathology (such as a follicular or papillary thyroid neoplasm) may cause the destruction of thyroid parenchyma, leading to chronic TSH oversecretion, which stimulates both follicular and C cells [2].…”

Section: Classificationmentioning

confidence: 99%

“…For a long time, the coexistence of CCH and MTC within the thyroid parenchyma has been considered as an indicator of MEN2 [42] and CCH has been viewed as a preneoplastic stage of C cell disease (neoplastic CCH, see above) [28]. The progression from CCH to MTC has been recognized as a well-defined event in the familial setting, including familial MTC and MEN2 syndrome [32,38,43]; thus, recognition of specific genetic changes allowed prophylactic thyroidectomy to be performed at an early stage of this evolution, thereby preventing the progression of the C cell disease to MTC [37].…”

Section: Clinical Significance and Managementmentioning

confidence: 99%

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Incidental Thyroid C Cell Hyperplasia: Clinical Significance and Implications in Practice

et al. 2015

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Incidental C cell hyperplasia (CCH) following thyroidectomy for other indications may rarely be encountered, which may raise concerns about its clinical significance and proper management. CCH can be classified as physiological (reactive) or neoplastic. Reactive CCH has no malignant potential and can be observed in association with many other thyroid diseases (including differentiated thyroid cancer); in contrast, neoplastic CCH should be considered as a preneoplastic stage in the spectrum of C cell disease, ultimately leading to the development of medullary thyroid cancer (MTC). Neoplastic CCH is commonly observed in patients with germ-line mutations in the RET oncogene (commonly in families with a history of hereditary MTC, i.e. familial MTC or multiple endocrine neoplasia type 2 (MEN2)). CCH should be considered in patients with hypercalcitoninemia without nodular thyroidopathy. Total thyroidectomy, which is commonly performed for the majority of thyroid diseases, is an adequate treatment and achieves cure, even in patients with neoplastic CCH. There is no role for cervical lymph node dissection in patients with pure CCH. In conclusion, reactive CCH has no malignant potential, in contrast to neoplastic CCH. Total thyroidectomy achieves cure of patients with CCH.

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Association of RET codon 691 polymorphism in radiation-induced human thyroid tumours with C-cell hyperplasia in peritumoural tissue

Cited by 16 publications

References 49 publications

RET gene mutations and polymorphisms in medullary thyroid carcinomas in Indian patients

RET gene mutations and polymorphisms in medullary thyroid carcinomas in Indian patients

The G691S RET Polymorphism Increases Glial Cell Line–Derived Neurotrophic Factor–Induced Pancreatic Cancer Cell Invasion by Amplifying Mitogen-Activated Protein Kinase Signaling

Incidental Thyroid C Cell Hyperplasia: Clinical Significance and Implications in Practice

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