A new germlineVHLgene mutation in three patients with apparently sporadic pheochromocytoma

2013 ◽  
Vol 78 (3) ◽  
pp. 391-397 ◽  
Author(s):  
Angela V. D'Elia ◽  
Franco Grimaldi ◽  
Stefano Pizzolitto ◽  
Giovanna De Maglio ◽  
Elisa Bregant ◽  
...  
Keyword(s):  
Sporadic Pheochromocytoma

Comparative study between familial and sporadic pheochromocytoma

2018 ◽  
Author(s):  
Paula Garcia-Sancho ◽  
Agustina P. Marengo ◽  
Fernando Guerrero ◽  
Inmaculada Peiro ◽  
Elisa Santacruz ◽  
...  
Keyword(s):  
Comparative Study ◽  
Sporadic Pheochromocytoma

scholarly journals Frequent EPAS1/HIF2α exons 9 and 12 mutations in non-familial pheochromocytoma

2014 ◽  
Vol 21 (3) ◽  
pp. 495-504 ◽  
Author(s):  
Jenny Welander ◽  
Adam Andreasson ◽  
Michael Brauckhoff ◽  
Martin Bäckdahl ◽  
Catharina Larsson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
Gene Expression Pattern ◽  
Exon 2 ◽  
Dna And Rna ◽  
Familial Pheochromocytoma ◽  
Predisposing Genes ◽  
Adrenal Pheochromocytoma ◽  
New Gene ◽  
Sporadic Pheochromocytoma

Pheochromocytomas are neuroendocrine tumors arising from the adrenal medulla. While heritable mutations are frequently described, less is known about the genetics of sporadic pheochromocytoma. Mutations in genes involved in the cellular hypoxia response have been identified in tumors, and recentlyEPAS1, encoding HIF2α, has been revealed to be a new gene involved in the pathogenesis of pheochromocytoma and abdominal paraganglioma. The aim of this study was to further characterizeEPAS1alterations in non-familial pheochromocytomas. Tumor DNA from 42 adrenal pheochromocytoma cases with apparently sporadic presentation, without known hereditary mutations in predisposing genes, were analyzed for mutations inEPAS1by sequencing of exons 9 and 12, which contain the two hydroxylation sites involved in HIF2α degradation, and also exon 2. In addition, the copy number at theEPAS1locus as well as transcriptome-wide gene expression were studied by DNA and RNA microarray analyses, respectively. We identified six missenseEPAS1mutations, three in exon 9 and three in exon 12, in five of 42 pheochromocytomas (12%). The mutations were both somatic and constitutional, and had no overlap in 11 cases (26%) with somatic mutations inNF1orRET. One sample had two differentEPAS1mutations, shown by cloning to occur incis, possibly indicating a novel mechanism of HIF2α stabilization through inactivation of both hydroxylation sites. One of the tumors with anEPAS1mutation also had a gain in DNA copy number at theEPAS1locus. AllEPAS1-mutated tumors displayed a pseudo-hypoxic gene expression pattern, indicating an oncogenic role of the identified mutations.

Rationalization of Genetic Testing in Patients with Apparently Sporadic Pheochromocytoma/Paraganglioma

2009 ◽  
Vol 41 (09) ◽  
pp. 672-675 ◽  
Author(s):  
A. Cascón ◽  
E. López-Jiménez ◽  
I. Landa ◽  
S. Leskelä ◽  
L. Leandro-García ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Sporadic Pheochromocytoma

scholarly journals Analysis of SDHAF3 in familial and sporadic pheochromocytoma and paraganglioma

BMC Cancer ◽  
2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Trisha Dwight ◽  
Un Na ◽  
Edward Kim ◽  
Ying Zhu ◽  
Anne Louise Richardson ◽  
...  
Keyword(s):  
Sporadic Pheochromocytoma

scholarly journals Should genetic testing be performed in each patient with sporadic pheochromocytoma at presentation?

2009 ◽  
Vol 160 (2) ◽  
pp. 227-231 ◽  
Author(s):  
Pascal Pigny ◽  
Catherine Cardot-Bauters ◽  
Christine Do Cao ◽  
Marie Christine Vantyghem ◽  
Bruno Carnaille ◽  
...  
Keyword(s):  
Family History ◽  
Genetic Screening ◽  
Age Of Onset ◽  
Age At Onset ◽  
Hereditary Disease ◽  
Imaging Features ◽  
Systematic Screening ◽  
Bilateral Pheochromocytoma ◽  
Sporadic Pheochromocytoma ◽  
Hereditary Pheochromocytoma

BackgroundAccording to previous studies, around 15% of patients with an apparently sporadic pheochromocytoma and a negative family history had a hereditary disease. This high frequency together with the financial support provided to reference laboratories of molecular genetics by the French government led to a nearly systematic screening in each patient with a pheochromocytoma.ObjectiveTo check the efficiency of systematic genetic screening in patients with apparently sporadic pheochromocytoma, by analysing the 6 years experience of a multidisciplinary team in this field.MethodsOne hundred patients with a pheochromocytoma-only phenotype and no family history were included. Patients with extra-adrenal tumours were excluded. Prevalence of hereditary forms was determined and analyzed according to age at onset, sex. Cost of the genetic analysis was calculated.ResultsA germline mutation in one of the five susceptibility genes (VHL, RET, SDHD, SDHC, SDHB) was identified in eight patients (8%) with an age of onset between 13 and 57 years. Among them, six had a bilateral pheochromocytoma and only two had a unilateral tumour. If the guidelines for genetic screening were age of onset less than 50 or bilateral pheochromocytoma, no patients with a hereditary tumour would be missed and a 24% cost reduction would be achieved.ConclusionsAccording to these data, a genetic predisposition test for hereditary pheochromocytoma seems not recommended in patients with a unilateral adrenal tumour diagnosed after 50 in the absence of familial, clinical, biological or imaging features for a familial disease.

scholarly journals Somatic Mutations in H-RAS in Sporadic Pheochromocytoma and Paraganglioma Identified by Exome Sequencing

2013 ◽  
Vol 98 (7) ◽  
pp. E1266-E1271 ◽  
Author(s):  
Joakim Crona ◽  
Alberto Delgado Verdugo ◽  
Rajani Maharjan ◽  
Peter Stålberg ◽  
Dan Granberg ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Signaling Pathway ◽  
Somatic Mutations ◽  
Predictive Marker ◽  
Erk Signaling ◽  
Illumina Hiseq ◽  
Ras Mutations ◽  
Mutational Status ◽  
Whole Exome ◽  
Sporadic Pheochromocytoma

Context: Up to 60% of pheochromocytoma (PCC) and paraganglioma (PGL) are associated with either somatic or germline mutations in established PCC and PGL susceptibility loci. Most unexplained cases are characterized by an increased activity of the RAS/RAF/ERK signaling pathway. Mutations in RAS subtypes H, K, and N are common in human cancers; however, previous studies have been inconsistent regarding the mutational status of RAS in PCC and PGL. Objectives: The aim of this study was to identify novel disease causing genes in PCC and PGL tumors. Design, setting, and participants: Four benign and sporadic PCC and PGL tumors were subjected to whole exome sequencing using the Illumina HiSeq Platform. Sequences were processed by CLC genomics 4.9 bioinformatics software and the acquired list of genetic variants was filtered against the Catalogue of Somatic Mutations in Cancer database. Findings were validated in an additional 78 PCC and PGL tumor lesions. Results: Exome sequencing identified 2 cases with somatic mutations in the H-RAS. In total, 6.9% (n = 4/58) of tumors negative for mutations in major PCC and PGL loci had mutations in H-RAS: G13R, Q61K, and Q61R. There were 3 PCC and 1 PGL; all had sporadic presentation with benign tumor characteristics and substantial increases in norepinephrine and/or epinephrine. H-RAS tumors were exclusively found in male patients (P = .007). Conclusions: We identified recurrent somatic H-RAS mutations in pheochromocytoma and paraganglioma. Tumors with H-RAS mutations had activation of the RAS/RAF/ERK signaling pathway and were associated with male PCC patients having benign and sporadic disease characteristics. H-RAS could serve as a prognostic and predictive marker as well as a novel therapeutic target.

scholarly journals Should Patients with Apparently Sporadic Pheochromocytomas or Paragangliomas be Screened for Hereditary Syndromes?

2006 ◽  
Vol 91 (8) ◽  
pp. 2851-2858 ◽  
Author(s):  
Camilo Jiménez ◽  
Gilbert Cote ◽  
Andrew Arnold ◽  
Robert F. Gagel
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Evidence Synthesis ◽  
Germline Mutations ◽  
Potential Effect ◽  
Hereditary Disease ◽  
Mitochondrial Complex ◽  
Hereditary Syndromes ◽  
Sporadic Pheochromocytoma ◽  
Hereditary Pheochromocytoma

Abstract Context: The recent identification of germline mutations of the mitochondrial complex II genes in variants of paraganglioma/pheochromocytoma syndrome has enlarged the number of known causative genes for hereditary pheochromocytoma. A question confronting clinicians is whether they should screen patients with apparently sporadic pheochromocytomas for unsuspected germline mutations of some or all of the seven genes known to cause hereditary paraganglioma or pheochromocytoma (NF1, VHL, RET, MEN1, SDHD, SDHC, and SDHB). A positive answer was suggested by a report that placed the estimate of hereditary disease in apparently sporadic pheochromocytoma as high as 24%. Evidence Acquisition: We applied clinically useful criteria to a review of the literature, defining cases of apparently sporadic pheochromocytoma as those without a suspicious personal or family history, with a focal, unilateral pheochromocytoma, and presenting at age less than 50 yr. Evidence Synthesis: We reduced the overall estimate of unsuspected hereditary pheochromocytoma patients with apparently sporadic pheochromocytoma to approximately 17%. Mutations in only three genes (VHL, SDHB, and SDHD) accounted for almost this entire minority, and unsuspected RET mutation was rare. Costs, coverage by insurance, the potential effect on insurability, and deficient information for populations outside of referral centers should be considered before recommending genetic testing in patients with apparently sporadic presentations of pheochromocytomas. Conclusion: We recommend genetic testing for patients with an apparently sporadic pheochromocytoma under the age of 20 yr with family history or features suggestive of hereditary pheochromocytoma or for patients with sympathetic paragangliomas. For individuals who do not meet these criteria, genetic testing is optional.

Loss of Heterozygosity on Chromosomes 1p and 11p in Sporadic Pheochromocytoma

1989 ◽  
Vol 81 (5) ◽  
pp. 367-370 ◽  
Author(s):  
M. Tsutsumi ◽  
J. Yokota ◽  
T. Kakizoe ◽  
K. Koiso ◽  
T. Sugimura ◽  
...  
Keyword(s):  
Loss Of Heterozygosity ◽  
Sporadic Pheochromocytoma
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