Germline mutations in PTEN and SDHC in a woman with epithelial thyroid cancer and carotid paraganglioma

Zbuk, Kevin; Patócs, Attila; Shealy, Amy; Sylvester, Heather; Miesfeldt, Susan; Eng, Charis

doi:10.1038/ncponc0935

Cited by 28 publications

(22 citation statements)

References 15 publications

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“…On the contrary, the association of papillary thyroid carcinoma (PTC), the most common thyroid carcinoma, arising from the follicular cells, with single or multiple PGL/PHEO was reported [1][2][3][4][5][6][7][8] in only a few cases (Table 1). Whether this association is coincidental or has a genetic underlying relationship remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Coexistence of paraganglioma/pheochromocytoma and papillary thyroid carcinoma: a four-case series analysis

2015

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The paraganglioma (PGL)/pheochromocytoma (PHEO)-papillary thyroid carcinoma (PTC) dyad has been reported rarely. Whether the association is coincidental or results from an underlying genetic predisposition is difficult to ascertain. We analyzed clinical and molecular data on four unrelated patients identified and treated by one of us (MJB) at a tertiary center. Patients were screened for germline variants in a panel of candidate genes: RET, VHL, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, PTEN, CDKN1B. All patients were female; median age at diagnosis of PGL/PHEO was 45 years and at diagnosis of PTC was 49.5 years. Only one patient had family history of thyroid cancer. PTC was multifocal in 2 cases, of the classical type in 2 cases and of the follicular type in 2 cases. Two patients harbored heterozygous germline variants of uncertain significance in the SDHB gene: Ser163Pro and Ala3Gly. The -79T>C polymorphism in the CDKN1B gene was present in all patients (3 in homozygous and 1 in heterozygous state). Results deriving from a comprehensive analysis of a panel of genes suggest that there is no single explanation for the association PGL/PHEO-PTC. It may occur through different mechanisms such as the combinatorial effect of different genetic variants, be a coincidental association or, alternatively, result from genetic variants in genes still awaiting identification.

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Section: Introductionmentioning

confidence: 99%

Coexistence of paraganglioma/pheochromocytoma and papillary thyroid carcinoma: a four-case series analysis

2015

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“…Several other neoplasms have been reported in SDHx mutation carriers including papillary thyroid carcinoma (PTC), medullary thyroid carcinoma, pancreatic neuroendocrine tumor, adrenal cortical adenoma, neuroblastoma (NBL), ganglioneuroma (GN), adenomatoid tumor of the adrenal gland, melanoma, lung cancer, breast carcinoma, oesophageal cancer, rectal and ovarian carcinomas, uterine adenocarcinoma, uterine leiomyoma, testicular seminoma, bladder cancer, meningioma, oligodendroglioma, cecal polyps, and hematolymphoid malignancies (7,8,9,10,11,12,13,14,15,16,17,18,19).…”

Section: Introductionmentioning

confidence: 99%

Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC–PGL syndromes: a clinicopathological and molecular analysis

Papathomas

Gaal

Corssmit

et al. 2014

European Journal of Endocrinology

118

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Objective: Although the succinate dehydrogenase (SDH)-related tumor spectrum has been recently expanded, there are only rare reports of non-pheochromocytoma/paraganglioma tumors in SDHx-mutated patients. Therefore, questions still remain unresolved concerning the aforementioned tumors with regard to their pathogenesis, clinicopathological phenotype, and even causal relatedness to SDHx mutations. Absence of SDHB expression in tumors derived from tissues susceptible to SDH deficiency is not fully elucidated. Design and methods: Three unrelated SDHD patients, two with pituitary adenoma (PA) and one with papillary thyroid carcinoma (PTC), and three SDHB patients affected by renal cell carcinomas (RCCs) were identified from four European centers. SDHA/SDHB immunohistochemistry (IHC), SDHx mutation analysis, and loss of heterozygosity analysis of the involved SDHx gene were performed on all tumors. A cohort of 348 tumors of unknown SDHx mutational status, including renal tumors, PTCs, PAs, neuroblastic tumors, seminomas, and adenomatoid tumors, was investigated by SDHB IHC. Printed in Great BritainPublished by Bioscientifica Ltd.Conclusions: These findings strengthen the etiological association of SDHx genes with pituitary neoplasia and provide evidence against a link between PTC and SDHx mutations. Somatic deletions seem to constitute the second hit in SDHB-related renal neoplasia, while SDHx alterations do not appear to be primary drivers in sporadic tumorigenesis from tissues affected by SDH deficiency.

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“…We described a large Brazilian family that presents with PTC and/or GISTs, but no SDHx mutations were detected except for a rare genetic variant, which was shown to be nonpathogenic by in silico analysis. Although the SDH-related tumor spectrum has been recently expanded, there are only a few reports of nonpheochromocytoma/paraganglioma tumors in SDHx -mutated patients [14,31,32,33,34,35,36]. In particular, 1-5% of SDHB / SDHD mutation carriers with paragangliomas/pheochromocytomas were found to present renal cells or PTC [14].…”

Section: Discussionmentioning

confidence: 99%

Familiar Papillary Thyroid Carcinoma in a Large Brazilian Family Is Not Associated with Succinate Dehydrogenase Defects

et al. 2016

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Background: Thyroid cancer is the most common endocrine gland malignancy. Advances in understanding the genetic basis for thyroid cancer revealed the potential involvement of several genes in the formation of thyroid tumors. Mutations in the gene coding for succinate dehydrogenase subtype B (SDHB) have been implicated in papillary thyroid cancer (PTC). Succinate dehydrogenase (SDH) is a heterotetrameric protein composed of four subunits, SDHA,SDHB,SDHC, and SDHD, and participates in both the electron transport chain and the tricarboxylic acid cycle. The aim of the study was to evaluate the association between variants in the SDHA,SDHB,SDHC, and SDHD genes and familiar PTC in a large Brazilian family. Method: Four patients with PTC, 1 patient with PTC and gastrointestinal stromal tumor (GIST), 1 patient with GIST, and their relatives - several of them with different thyroid problems - from a large Brazilian family were screened for genetic variations of SDHx genes with the use of polymerase chain reaction-single-stranded conformational polymorphism and direct sequencing. Results: Only one rare variation in SDHA was found in some of the family members, but not segregating with the disease. No other genetic variants of these genes were detected in the family members that presented with PTC and/or GIST. Conclusion: Familiar PTC and a GIST were not associated with SDHx mutations; additional genetic defects, yet unknown, may be responsible for the development of tumor.

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Germline mutations in PTEN and SDHC in a woman with epithelial thyroid cancer and carotid paraganglioma

Cited by 28 publications

References 15 publications

Coexistence of paraganglioma/pheochromocytoma and papillary thyroid carcinoma: a four-case series analysis

Coexistence of paraganglioma/pheochromocytoma and papillary thyroid carcinoma: a four-case series analysis

Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC–PGL syndromes: a clinicopathological and molecular analysis

Familiar Papillary Thyroid Carcinoma in a Large Brazilian Family Is Not Associated with Succinate Dehydrogenase Defects

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