A founder SDHB mutation in Portuguese paraganglioma patients

Martins, Raquel G.; Nunes, Joana B.; Máximo, Valdemar; Soares, Paula; Peixoto, Joana; Catarino, Telmo; Rito, Teresa; Soares, Pedro; Pereira, Luı́sa; Sobrinho-Simões, Manuel; Santos, Ana Paula; Couto, Joana; Henrique, Rui; Matos-Loureiro, Joana; Dias, Paula; Torres, Isabel; Lima, Jorge

doi:10.1530/erc-12-0399

Cited by 15 publications

(7 citation statements)

References 9 publications

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“…8,10,11,58,59 Loss of SDHB protein expression is seen in pheochromocytomas/paragangliomas either harboring a mutation in any of the SDH genes or with somatic hypermethylation of the SDHC promoter region, 42 whereas loss of both SDHB and SDHA immunoreactivity is demonstrated only in the context of an SDHA mutation. [8][9][10][11][12][13][14][15][16][17][18][19][20] In agreement with previous studies, 8,10,11,[17][18][19][20] SDHB-/C-/D-and SDHAmutated tumors displayed the aforementioned and NF1 mutations, 8,10 respectively. By using a mouse monoclonal (21A11) SDHB antibody at a low concentration (1 in 1000), Gill et al 10 suggested that VHL-associated tumors could be classified as negative or weak diffuse rather than positive as demonstrated by a high concentration approach of two SDHB antibodies.…”

Section: Discussionsupporting

confidence: 91%

SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: a multicenter interobserver variation analysis using virtual microscopy: a Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T)

et al. 2015

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Section: Discussionsupporting

confidence: 91%

SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: a multicenter interobserver variation analysis using virtual microscopy: a Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T)

et al. 2015

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“…For instance, in VHL disease-associated pheochromocytoma, codon 167 of VHL gene appears as a first target, since missense mutations in this codon are strongly associated with pheochromocytoma development [60]. In addition, we should be aware of founder mutations already reported for SDHx genes in different countries such as the Netherlands, Poland, Italy, Spain, and Portugal in order to develop effective screening protocols [158–162]. …”

Section: Genetic Testing Strategy In Paraganglioma/pheochromocytomamentioning

confidence: 99%

Paragangliomas/Pheochromocytomas: Clinically Oriented Genetic Testing

Martins

Bugalho

2014

International Journal of Endocrinology

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Paragangliomas are rare neuroendocrine tumors that arise in the sympathetic or parasympathetic nervous system. Sympathetic paragangliomas are mainly found in the adrenal medulla (designated pheochromocytomas) but may also have a thoracic, abdominal, or pelvic localization. Parasympathetic paragangliomas are generally located at the head or neck. Knowledge concerning the familial forms of paragangliomas has greatly improved in recent years. Additionally to the genes involved in the classical syndromic forms: VHL gene (von Hippel-Lindau), RET gene (Multiple Endocrine Neoplasia type 2), and NF1 gene (Neurofibromatosis type 1), 10 novel genes have so far been implicated in the occurrence of paragangliomas/pheochromocytomas: SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, EGLN1, HIF2A, and KIF1B. It is currently accepted that about 35% of the paragangliomas cases are due to germline mutations in one of these genes. Furthermore, somatic mutations of RET, VHL, NF1, MAX, HIF2A, and H-RAS can also be detected. The identification of the mutation responsible for the paraganglioma/pheochromocytoma phenotype in a patient may be crucial in determining the treatment and allowing specific follow-up guidelines, ultimately leading to a better prognosis. Herein, we summarize the most relevant aspects regarding the genetics and clinical aspects of the syndromic and nonsyndromic forms of pheochromocytoma/paraganglioma aiming to provide an algorithm for genetic testing.

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“…Portugal has a relatively homogeneous population and several founder mutations or mutations with a founder effect have been described associated with cancer predisposition [28][29][30][31][32][33]. Our group has recently reported that the BRCA2 c.156_157insAlu rearrangement, a Portuguese founder mutation, and the BRCA1 c.3331_3334del mutation, which shows a founder effect in Portugal, represent 33.6 and 12.6 %, respectively, of HBOC families with pathogenic mutations, accounting for 57.1 % of BRCA2 and 30.6 % of BRCA1 deleterious mutations [33].…”

Section: Introductionmentioning

confidence: 99%

The role of germline mutations in the BRCA1/2 and mismatch repair genes in men ascertained for early-onset and/or familial prostate cancer

et al. 2015

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Prostate cancer (PrCa) is one of the most common cancers diagnosed worldwide and 5-10 % of all cases are estimated to be associated with inherited predisposition. Even though there is strong evidence that the genetic component is significant in PrCa, the genetic etiology of familial and early-onset disease is largely unknown. Although it has been suggested that men from families with hereditary breast/ovarian cancer (HBOC) and, more recently, with Lynch syndrome may have an increased risk for PrCa, the contribution of these syndromes to PrCa predisposition in families ascertained for early-onset and/or familial PrCa, independently of the presence of other cancers in the family, is uncertain. To quantify the contribution of genes associated with HBOC and Lynch syndromes to PrCa predisposition, we have tested for germline mutations 460 early-onset and/or familial PrCa patients. All patients were screened for the six mutations that are particularly common in Portugal and 38 of them were selected for complete sequencing of BRCA1/2 and/or MLH1, MSH2 and MSH6. Two patients were found to harbor the same MSH2 mutation and a third patient carried a Portuguese BRCA2 founder mutation. None of the alterations were identified in 288 control subjects. Furthermore, we reviewed the 62 PrCa diagnoses in all HBOC (n = 161) and Lynch syndrome (n = 124) families previously diagnosed at our department, and found five other BRCA2 mutation carriers and two additional MSH2 mutation carriers. The clinicopathological characteristics of mutation carriers are in concordance with earlier data suggesting an aggressive PrCa phenotype and support the hypothesis that mutation carriers might benefit from targeted screening according to the gene mutated in the germline.

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A founder SDHB mutation in Portuguese paraganglioma patients

Cited by 15 publications

References 9 publications

SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: a multicenter interobserver variation analysis using virtual microscopy: a Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T)

SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: a multicenter interobserver variation analysis using virtual microscopy: a Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T)

Paragangliomas/Pheochromocytomas: Clinically Oriented Genetic Testing

The role of germline mutations in the BRCA1/2 and mismatch repair genes in men ascertained for early-onset and/or familial prostate cancer

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