The Succinate Dehydrogenase Genetic Testing in a Large Prospective Series of Patients with Paragangliomas

Burnichon, Nelly; Rohmer, V.; Amar, Laurence; Herman, Philippe; Leboulleux, Sophie; Darrouzet, V.; Niccoli, Patricia; Gaillard, Dominique; Chabrier, G.; Chabolle, F.; Coupier, Isabelle; Thiéblot, P; Lecomte, P.; Bertherat, Jérôme; Wion-Barbot, N.; Murat, A.; Vénisse, Annabelle; Plouin, Pierre‐François; Jeunemaı̂tre, Xavier; Gimenez-Roqueplo, Anne-Paule

doi:10.1210/jc.2008-2504

Cited by 333 publications

(353 citation statements)

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“…methods that are well-established for detection of these genetic lesions, such as MLPA, quantitative multiplex PCR or other genome-wide copy number analysis assays, can be performed 43,44 . Alternatively, targeted NGS panels can be designed to optimize detection of larger deletions, insertions or rearrangements, as reported in hereditary breast cancer diagnostic panels 45 .…”

Section: Box 1 | Features Unique To Ppglsmentioning

confidence: 99%

Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas

et al. 2016

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Phaeochromocytomas and paragangliomas (PPGLs) are neural-crest-derived tumours of the sympathetic or parasympathetic nervous system that are often inherited and are genetically heterogeneous. Genetic testing is recommended for patients with these tumours and for family members of patients with hereditary forms of PPGLs. Due to the large number of susceptibility genes implicated in the diagnosis of inherited PPGLs, next-generation sequencing (NGS) technology is ideally suited for carrying out genetic screening of these individuals. This Consensus Statement, formulated by a study group comprised of experts in the field, proposes specific recommendations for the use of diagnostic NGS in hereditary PPGLs. In brief, the study group recommends target gene panels for screening of germ line DNA, technical adaptations to address different modes of disease transmission, orthogonal validation of NGS findings, standardized classification of variant pathogenicity and uniform reporting of the findings. The use of supplementary assays, to aid in the interpretation of the results, and sequencing of tumour DNA, for identification of somatic mutations, is encouraged. In addition, the study group launches an initiative to develop a gene-centric curated database of PPGL variants, with annual re-evaluation of variants of unknown significance by an expert group for purposes of reclassification and clinical guidance.

Funding Agencies|Cancer Prevention and Research Institute of Texas (CPRIT) [RP101202, RP57154]; Department of Defense [CDMRP W81XWH-12-1-0508]; Voelcker Fund; National Institutes of Health (NIH)s National Center for Research Resources; National Center for Advancing Translational Sciences [8UL1TR000149]; INSERM; French National Cancer Institute (INCA); Direction Generale de lOffre de Soins (DGOS); INCA [INCA-DGOS_8663]; European Union [633983]; Brazilian National Council for Scientific and Technological Development (CNPq); Cancer Research for PErsonalized Medicine (CARPEM); ERC Advanced Researcher Award

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Section: Box 1 | Features Unique To Ppglsmentioning

confidence: 99%

Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas

et al. 2016

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“…The mean age at diagnosis of an HNPGL in this cohort (45·9 years) was higher than that reported previously, of between 30 and 37 years8 10, 18. In the Netherlands, tumour screening in SDHB ‐linked families is advised from the age of 18 years onwards.…”

Section: Discussionmentioning

confidence: 56%

Nationwide study of patients with head and neck paragangliomas carrying SDHB germline mutations

et al. 2018

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BackgroundGermline mutations in the succinate dehydrogenase B (SDHB) gene predispose to hereditary paraganglioma (PGL) syndrome type 4. The aim of this study was to evaluate the clinical characteristics and outcome of treatment strategies for patients with head and neck paraganglioma (HNPGL) carrying SDHB germline mutations.MethodsThis was a retrospective evaluation of patients with HNPGL carrying SDHB germline mutations in the Netherlands.ResultsIn a Dutch nationwide cohort study of SDHB germline mutation carriers, 54 patients with a total of 62 HNPGLs were identified. Forty‐one of 54 patients (76 per cent) visited the outpatient clinic because of associated complaints. Eight patients (15 per cent) had multiple PGLs. One patient (2 per cent) developed a phaeochromocytoma and three (6 per cent) developed a malignant PGL. Twenty‐seven patients (50 per cent) had an operation for their HNPGL and 15 (28 per cent) received radiotherapy. Three patients with HNPGL (6 per cent) were diagnosed with additional non‐paraganglionic tumours.ConclusionIf an SDHB germline mutation is identified in a patient with HNPGL, the clinician should be aware of the variable manifestations of the SDHB‐linked tumour syndrome, the risk of catecholamine excess, concurrent phaeochromocytoma, and association with non‐paraganglionic tumours.

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“…При всех SDHx-мутациях могут встре-чаться феохромоцитома, параганглиома, в том числе головы и шеи, а также другие опухоли (табл. 6) [41][42][43]. Примечание.…”

Section: тип мутацииunclassified

Personalized diagnostics of chromaffin tumors (pheochromocytoma, paraganglioma) in oncoendocrinology

et al. 2018

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Central Military Clinical Hospital named after P.V. Mandryko, Moscow, Russian FederationФеохромоцитомы и параганглиомы (ФХ/ПГ) -редкие катехоламин-секретирующие нейроэндокринные опухоли, почти в 40% случаев имеющие наследственную природу. Заболеваемость колеблется от 2 до 8 случаев на 1 млн человек в год, с пиком заболеваемости в 30-50 лет. Согласно последней классификации, хромаффинные опухоли отнесены к злокачественным новообразованиям. Частота метастазирования ФХ -10%, ПГ -25%. Клинические проявления ФХ и ПГ обусловлены избытком катехоламинов. Известно более 20 наследуемых генов, мутации в которых провоцируют развитие ФХ/ПГ. С точки зрения молекулярной клеточной патофизиологии известный на сегодня пул мутаций можно разделить на два кластера: первый (SDHх, SDHAF2 -фактор сборки SDH, FH, MDH2) нарушает функционирование цикла Кребса и энергетической транспортной цепи митохондрий, второй (RET, NF1, TMEM127, MAX) -мутации генов рецепторов трансмембранных белков-протеинкиназ (тирозинкиназ), активирующие внутриклеточные сигнальные пути (PI3K-AKT-mTOR и MYC), ответственные за клеточный рост, регуляцию роста и дифференцировку клеток. В итоге происходят стабилизация HIF-транскрипционных факторов (оксидативный стресс), изменение метилирования ДНК, приводящие в итоге к глубоким нарушениям экспрессии генов и опухолевой трансформации клетки. Выделяют три основных секреторно-биохимических фенотипа ФХ/ПГ: норадренергический, адренергический и допаминергический. В зависимости от типа секреции опухоли, возраста пациента и семейного анамнеза назначаются комплементарные генетические исследования и методы молекулярной визуализации. В клинической практике биохимический фенотип опухоли, стадия, семейный анамнез и особенно генетический "паспорт" опухоли позволяют подобрать оптимальный алгоритм молекулярной визуализации (ОФЭКТ/ПЭТ) в целях персонализации тактики лечения и клинического прогноза.Ключевые слова : хромаффинные опухоли, феохромоцитома, параганглиома, радионуклидная диагностика, молекулярная визуализация, генетика, эндокринология, онкология, радиология, онкоэндокринология. Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-secreting neuroendocrine tumours, up to 40% of which occur in the setting of a hereditary syndrome. The incidence is 2 to 8 per million persons per year. The peak incidence occurs in the third to fifth decades of life. According to the most recent classification, chromaffin tumours refer to malignant neoplasms. The incidence of metastasis in pheochromocytomas is 10%; in paragangliomas it is 25%. Clinical manifestations of PPGLs are caused by the excess of catecholamines. More than 20 hereditary gene mutations are known to result in PPGLs development. According to the molecular and cellular pathophysiology, all currently known mutations can be divided intoThe article can used under the CC BY-NC-ND 4.0 license. Статья может быть использована на условиях международной лицензии CC BY-NC-ND 4.0.

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The Succinate Dehydrogenase Genetic Testing in a Large Prospective Series of Patients with Paragangliomas

Abstract: SDH genetic testing, including tests for large genomic deletions, is indicated in all patients with head and neck and/or thoracic-abdominal or pelvic paraganglioma and can be targeted according to clinical criteria.

Cited by 333 publications

References 26 publications

Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas

Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas

Nationwide study of patients with head and neck paragangliomas carrying SDHB germline mutations

Personalized diagnostics of chromaffin tumors (pheochromocytoma, paraganglioma) in oncoendocrinology

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