scholarly journals Vandetanib in a child affected by neurofibromatosis type 1 and medullary thyroid carcinoma with both NF1 and homozygous RET proto-oncogen germ-line mutations

2020 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Begumhan Demir Gundogan ◽  
Fatih Sagcan ◽  
Sevcan Tug Bozdogan ◽  
Yuksel Balci ◽  
Ferah Tuncel Daloglu ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Neurofibromatosis Type 1 ◽  
Germ Line ◽  
Neurofibromatosis Type ◽  
Medullary Thyroid ◽  
Germ Line Mutations

scholarly journals Next-generation panel sequencing identifies NF1 germline mutations in three patients with pheochromocytoma but no clinical diagnosis of neurofibromatosis type 1

2018 ◽  
Vol 178 (2) ◽  
pp. K1-K9 ◽  
Author(s):  
Laura Gieldon ◽  
Jimmy Rusdian Masjkur ◽  
Susan Richter ◽  
Roland Därr ◽  
Marcos Lahera ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Clinical Diagnosis ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Germline Mutations ◽  
Next Generation ◽  
Medullary Thyroid

Objective Our objective was to improve molecular diagnostics in patients with hereditary pheochromocytoma and paraganglioma (PPGL) by using next-generation sequencing (NGS) multi-gene panel analysis. Derived from this study, we here present three cases that were diagnosed with NF1 germline mutations but did not have a prior clinical diagnosis of neurofibromatosis type 1 (NF1). Design We performed genetic analysis of known tumor predisposition genes, including NF1, using a multi-gene NGS enrichment-based panel applied to a total of 1029 PPGL patients. We did not exclude genes known to cause clinically defined syndromes such as NF1 based on missing phenotypic expression as is commonly practiced. Methods Genetic analysis was performed using NGS (TruSight Cancer Panel/customized panel by Illumina) for analyzing patients’ blood and tumor samples. Validation was carried out by Sanger sequencing. Results Within our cohort, three patients, who were identified to carry pathogenic NF1 germline mutations, attracted attention, since none of the patients had a clinical suspicion of NF1 and one of them was initially suspected to have MEN2A syndrome due to co-occurrence of a medullary thyroid carcinoma. In these cases, one splice site, one stop and one frameshift mutation in NF1 were identified. Conclusions Since phenotypical presentation of NF1 is highly variable, we suggest analysis of the NF1 gene also in PPGL patients who do not meet diagnostic NF1 criteria. Co-occurrence of medullary thyroid carcinoma and PPGL was found to be a clinical decoy in NF1 diagnostics. These observations underline the value of multi-gene panel NGS for PPGL patients.

Medullary thyroid carcinoma in two patients with neurofibromatosis type 1

2019 ◽  
Author(s):  
Pollet Emily ◽  
Martens Broes ◽  
Van Haecke Helena ◽  
Sajevets Tatjana ◽  
Van den Bruel Annick
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Medullary Thyroid

scholarly journals Screening of six risk exons of the RET proto-oncogene in families with medullary thyroid carcinoma in the Czech Republic

2004 ◽  
Vol 183 (2) ◽  
pp. 257-265 ◽  
Author(s):  
Š Jindřichová ◽  
J Včelák ◽  
P Vlček ◽  
M Neradilová ◽  
J Němec ◽  
...  
Keyword(s):  
Czech Republic ◽  
Genetic Testing ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Germ Line ◽  
Molecular Genetic ◽  
The Czech Republic ◽  
Medullary Thyroid ◽  
Germ Line Mutations ◽  
Exon 11

Medullary thyroid carcinoma (MTC) occurs as a sporadic form (75%) or as an autosomal dominant inherited familial disorder (25%) called familial MTC (FMTC) or as multiple endocrine neoplasia type 2 (MEN2) syndromes. Germ-line mutations in the rearranged during transfection (RET) proto-oncogene in exons 10, 11, 13, 14, 15 and 16 are known to be a cause of most of the familial forms. In this paper we report molecular genetic testing of 106 families with MTC (358 tested persons) from the Czech Republic in which we directly sequenced these six exons of the RET proto-oncogene. We detected germ-line mutations in 100% of MEN2B families (4/4 families), 90% of MEN2A families (9/10), 40% of FMTC families (4/10) and 7% of apparently sporadic MTC (6/82). Eleven different germ-line mutations were revealed. MEN2B was associated with mutation Met918 Thr in exon 16. In one MEN2B family beside this mutation the Tyr791 Phe was also found, which has not yet been reported. MEN2A was restricted to different mutations in exon 11 (codon 634). In FMTC and ‘sporadic’ MTC families the mutations in exons 10, 11, 13 and 14 were detected. The genotype/phenotype correlations are given. Genetic testing revealed germ-line mutations in 23 index patients, 24 family members and excluded them in 53 relatives.

Patient affected by neurofibromatosis type 1 and thyroid C-cell hyperplasia harboring pathogenic germ-line mutations in both NF1 and RET genes

Gene ◽  
2014 ◽  
Vol 536 (2) ◽  
pp. 332-335 ◽  
Author(s):  
Tonino Ercolino ◽  
Roberta Lai ◽  
Valentino Giachè ◽  
Salvatore Melchionda ◽  
Massimo Carella ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Germ Line ◽  
Neurofibromatosis Type ◽  
Cell Hyperplasia ◽  
C Cell Hyperplasia ◽  
C Cell ◽  
Germ Line Mutations

Neurofibromatosis Type 1 Due to Germ-Line Mosaicism in a Clinically Normal Father

1994 ◽  
Vol 331 (21) ◽  
pp. 1403-1407 ◽  
Author(s):  
Conxi Lazaro ◽  
Anna Ravella ◽  
Antonia Gaona ◽  
Victor Volpini ◽  
Xavier Estivill
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Germ Line ◽  
Neurofibromatosis Type ◽  
Clinically Normal ◽  
Normal Father

RET oncogene mutations in a large Korean kindred with familial medullary thyroid carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6066-6066
Author(s):  
Y. Lee ◽  
H. Park ◽  
J. Jung ◽  
Y. Lim ◽  
S. Uchino
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Germ Line ◽  
Radical Neck Dissection ◽  
Gene Mutations ◽  
Large Family ◽  
Carrier Status ◽  
Medullary Thyroid ◽  
Familial Medullary Thyroid Carcinoma ◽  
The Family

6066 Background: Familial medullary thyroid carcinoma (FMTC) is related to germ-line mutations in the RET proto-oncogene. The mutations concern mainly cystein residues in exons 10 and 11, whereas noncystein mutations in exons 13–16 are rare. These mutations have been recorded in the different populations, but to date there is no corresponding study in Korean families. In this study, we identify the RET mutations in the Korean family with FMTC and propose therapeutic approach in managing the disorder. Methods: The large family consists of 4 generations with a total of 32 individuals. There was a history of MTC in five members of the family. The index case was a 67-yr- old woman who underwent total thyroidectomy and both modified radical neck dissection in our hospital at the age of 48. We analysed exons 10, 11, 13, 14, 15 and 16 in index patients using DNA sequencing. Twenty-nine subjects from the family were clinically assessed and subsequently molecularly analysed for the presence of RET gene mutations. Results: We have found a missense TGC?AGC mutation at codon 618 in Exon 10. This transversion leads to the substitution of cystein with serin. The mutation was detected in all five MTC patients as well as in 6 asymptomatic relatives. The mutation shows a wide clinical heterogenecity, as there are carrier patients with age of diagnosis ranging from 9 to 64 years. Conclusions: It is likely that the mutation causes FMTC, because no other mutation was found in RET. This study showed 100% accordance between presence of the disease and gene carrier status is reported. Total preventive thyroidectomy has been recommended in all carriers of RET genetic defects. No significant financial relationships to disclose.

scholarly journals Polymorphisms in Exon 13 and Intron 14 of the RET Protooncogene: Genetic Modifiers of Medullary Thyroid Carcinoma?

2005 ◽  
Vol 90 (11) ◽  
pp. 6232-6236 ◽  
Author(s):  
S. M. Baumgartner-Parzer ◽  
R. Lang ◽  
L. Wagner ◽  
G. Heinze ◽  
B. Niederle ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Germ Line ◽  
Elevated Serum ◽  
Control Group ◽  
Serum Concentrations ◽  
Genetic Modifiers ◽  
Cycle Sequencing ◽  
Medullary Thyroid ◽  
Ret Protooncogene

Abstract Context: Single-nucleotide polymorphisms (SNPs) of the RET protooncogene (RET) could modify disease susceptibility and clinical phenotype in patients with sporadic or familial medullary thyroid carcinoma (FMTC). Objective/Design of the Study: Because frequencies of RET SNPs have not yet been evaluated in patients with elevated serum concentrations of calcitonin (hCt), a biochemical marker for medullary thyroid carcinoma (MTC), we studied RET SNPs in patients with FMTC (n = 22), patients with sporadic MTC (n = 45), and 71 subjects presenting with moderately elevated hCt concentrations (basal, >10 pg/ml; pentagastrin stimulated, > 50 < 100 pg/ml) in comparison with an age- and gender-matched control group (n = 79) with basal hCt concentrations in the normal range (<5 pg/ml). Methods: After DNA extraction from citrated whole blood, RET exons 10, 11, 13, 14, 15, and 16 and exon/intron boundaries were analyzed by PCR-based cycle sequencing for RET germ line mutations, exonic (G691S, L769L, S836S, S904S) and intronic (IVS13+158; NCBI rs2472737 = IVS14–24) SNPs. Results: In FMTC patients, the F791Y mutation was found to be associated (P = 0.001) with the L769L SNP. The exonic SNPs (G691S, L769L, S836S, and S904S) were not different among the four groups. The intron 14 SNP (IVS14–24), however, was more frequent in individuals with elevated hCt serum concentrations (P = 0.016) and patients with sporadic MTC (P < 0.001) when compared with the control group. Conclusions: These data suggest that the exon 13 (L769L) and the intron 14 (IVS14–24) SNPs could act as genetic modifiers in the development of some forms of hereditary and sporadic MTC, respectively.

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