Vandetanib in a Child Affected by Neurofibromatosis Type 1 and Medullary Thyroid Carcinoma with Both &lt;i&gt;NF1&lt;/i&gt; and Homozygous &lt;i&gt;RET&lt;/i&gt; Proto-oncogen Germ-line Mutations

Gündoğan, Begümhan Demir; Sağcan, Fatih; Bozdoğan, Sevcan Tuğ; Balcı, Yüksel; Daloglu, Ferah Tuncel; Çıtak, Elvan Çağlar

doi:10.4274/jcrpe.galenos.2020.2020.0051

Cited by 5 publications

(3 citation statements)

References 30 publications

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“…While it was determined that there was a decrease in visual field in 4 patients with asymptomatic optic glioma in the follow-up period; symptomatic two patients presented with decreased vision. The case with medullary thyroid carcinoma was in the familial NF1 group and had germ-line homozygous RET proto-oncogene mutation in addition to NF1 gene mutation (13).…”

Section: Resultsmentioning

confidence: 99%

Clinical findings and mutational spectrum of neurofibromatosis type 1 patients in a single center of south part of Turkey

Gündoğan¹,

Bozdoğan²,

Ayhan³

et al. 2021

Turk J Med Sci

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Aim:The aim of this study is to determine the mutation spectrums and clinical characteristics of NF1 patients followed up in our center and to investigate whether there is a genotype-phenotype relationship.Material and Methods: Sixty-three children and 34 relatives diagnosed with NF1 were included in the study. Age, gender, family history, clinical features, tumors detected in the patient at the time of diagnosis or during follow-up, orbital and cerebral magnetic resonance imaging (MRI) findings were recorded. Also results of the NF1 gene analysis results were recorded.Results: Fifty-three different mutations were found as a result of the NF1 gene analysis studied from patients and their family members. Among these 53 mutations, stop codon mutation was the most frequently detected mutations. Sixteen out of 50 (32%) mutations were found to be novel mutations. Twenty-eight tumors developed in our patients. Twenty of them were optic gliomas and others were medullary thyroid carcinoma, glioblastome multiforme, pons glioma, acute lymphoblastic leukemia, pilocytic astrositoma, hypothalamic glioma, cerebral hamartoma and cardiac fibroma.No genotype-phenotype relationship was detected in patients Conclusion: Comprehensive mutation analysis of NF1 will increase our knowledge due to its different phenotypic characteristics even in the same mutation.

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Section: Resultsmentioning

confidence: 99%

Clinical findings and mutational spectrum of neurofibromatosis type 1 patients in a single center of south part of Turkey

Gündoğan¹,

Bozdoğan²,

Ayhan³

et al. 2021

Turk J Med Sci

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“…MTC has been associated with NF1 but up to recent reports, it was unclear whether these tumors were caused by a second hit of the NF1 gene. There are few reports demonstrating association of MTC with NF1, and while most of these reports did not include germline or somatic genetic analysis, at least 2 studies identified both RET and NF1 germline variants in the same patients [ 38-41 ].…”

Section: Discussionmentioning

confidence: 99%

Not Only RET but NF1 and Chromosomal Instability Are Seen in Young Patients with Sporadic Medullary Thyroid Carcinoma

Castroneves,

Mangone,

Lerario

et al. 2024

Journal of the Endocrine Society

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Genetic analysis of sporadic Medullary Thyroid Carcinoma (MTC) has revealed somatic variants in RET, RAS, and occasionally other genes. However, around 20% of sporadic MTC patients lack a known genetic driver. To uncover potential new somatic or germline drivers we analyze a distinct cohort of patients with sporadic, very early-onset and aggressive MTC. Germline and somatic DNA exome sequencing was performed in 19 patients, previously tested negative for germline RET variants. Exome sequencing of 19 germline samples confirmed the absence of RET and identified an NF1 pathogenic variant in one patient. Somatic sequencing was successful in 15 tumors revealing RET variants in 80%, predominantly p.Met918Thr which was associated with disease aggressiveness. In RET-negative tumors, pathogenic variants were found in HRAS and NF1. The NF1 germline and somatic variants were observed in a patient without a prior clinical diagnosis of Neurofibromatosis type 1, demonstrating that the loss of heterozygosity of NF1 functions as a potential MTC driver. Somatic copy number alterations analysis revealed chromosomal alterations in 53.3% of tumors, predominantly in RET-positive cases, with losses in chromosomes 9 and 22 being the most prevalent. This study reveals that within a cohort of early-onset non-hereditary MTC, RET remains the major driver gene. In RET-negative tumors, NF1 and RAS are drivers of sporadic MTC. In addition, in young patients without a RET germline mutation, a careful clinical evaluation with a consideration of germline NF1 gene analysis is ideal to exclude Neurofibromatosis type 1.

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“…Interestingly, 1 patient in our cohort was diagnosed with thyroid medullary carcinoma and another with primary hyperparathyroidism. The association of these endocrine diseases and NF1 has been described in a few case reports [ 9 , 39 , 40 ], but the pathophysiologic link has not been proven. Unfortunately, we could not analyze the tumor of the patients to look for a second hit in the NF1 gene as observed for tumor suppressor genes and reported in tumor-related NF1 [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Endocrine Manifestations and GIST in 108 Systematically Screened Patients With Neurofibromatosis Type 1

Dupuis

Chevalier

Cardot-Bauters

et al. 2023

Journal of the Endocrine Society

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Introduction In NF1 patients, guidelines suggest screening for pheochromocytoma by metanephrine measurement and abdominal imaging, that may lead to the discovery of gastroenteropancreatic neuroendocrine tumors (GEP-NET) and their differential diagnosis, gastro-intestinal stromal tumors (GIST). Other endocrine manifestations such as follicular thyroid carcinoma and primary hyperparathyroidism have also been reported in a few cases. This study aimed to describe prevalence and clinical presentation of these manifestations through a systematic screening in a large cohort of patients. Patients and Methods In this monocentric retrospective study, 108 NF1 patients were included and screened for endocrine manifestations and GIST. Clinical, laboratory, molecular profile, pathology and morphologic (abdominal CT-scan and/or MRI) and functional imaging were collected. Results Twenty-four patients (22.2% of the cohort, 16 female, mean age 42.6 years) presented with pheochromocytomas that were unilateral in 65.5%, benign in 89.7%, and with a ganglioneural component in 20.7%. Three female patients (2.8% of the cohort, aged 42 to 63 years) presented with well-differentiated GEP-NET, and four (3.7%) with GIST. One patient had primary hyperparathyroidism, one patient had medullary microcarcinoma, and 16 patients had goiter, multinodular in 10 cases. There was no correlation between pheochromocytoma and other NF1 tumoral manifestations, nor correlations between pheochromocytoma and NF1 genotype, despite a familial clustering in one-third of patients. Discussion The pheochromocytoma prevalence in this NF1 cohort was higher (> 20%) than previously described, confirming the interest of systematic screening, especially in young women. The prevalence of GEP-NET and GIST was about 3%, respectively. No phenotype-genotype correlation was observed.

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Vandetanib in a Child Affected by Neurofibromatosis Type 1 and Medullary Thyroid Carcinoma with Both <i>NF1</i> and Homozygous <i>RET</i> Proto-oncogen Germ-line Mutations

Cited by 5 publications

References 30 publications

Clinical findings and mutational spectrum of neurofibromatosis type 1 patients in a single center of south part of Turkey

Clinical findings and mutational spectrum of neurofibromatosis type 1 patients in a single center of south part of Turkey

Not Only RET but NF1 and Chromosomal Instability Are Seen in Young Patients with Sporadic Medullary Thyroid Carcinoma

Prevalence of Endocrine Manifestations and GIST in 108 Systematically Screened Patients With Neurofibromatosis Type 1

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