Hereditary phaeochromocytomas and paragangliomas: a study of five susceptibility genes

Bauters, C.

doi:10.1136/jmg.40.6.e75

Cited by 64 publications

(40 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, if the decision criteria for genetic testing were age at onset less than 50 or bilateral pheochromocytoma, no patient with a hereditary tumour would be missed. In our cohort of patients, only 8% had a familial pheochromocytoma, a frequency strongly lower than the prevalence previously published in the 2002-2003 (4,5). This number is indeed also lower than the 12.7% prevalence recently reported by the European network for the study of adrenal tumours that broads together 545 patients with an apparently sporadic pheochro-mocytoma or a functional paraganglioma (6).…”

Section: Discussioncontrasting

confidence: 67%

“…However, exclusion of patients with a positive family history would decrease the rate of hereditary forms to 15.5% (4). In 2003, we reported a similar prevalence (15%) by studying simultaneously five susceptibility genes (the former and SDHC) in 13 index cases (5). At the same time in France, President J. Chirac implanted the 'Plan Cancer' whose aim number 22 was to improve the access to genetic testing by providing a…”

Section: Introductionmentioning

confidence: 86%

See 1 more Smart Citation

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

Pigny¹,

Cardot-Bauters²,

Cao³

et al. 2009

European Journal of Endocrinology

View full text Add to dashboard Cite

Background: According 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. Objective: To 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. Methods: One 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. Results: A 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. Conclusions: According 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.

show abstract

Section: Discussioncontrasting

confidence: 67%

Section: Introductionmentioning

confidence: 86%

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

Pigny¹,

Cardot-Bauters²,

Cao³

et al. 2009

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…We could not examine the gene for PGL-2, as it has yet to be identified, but we performed molecular genetic exclusion of SDHC mutation carriership (PGL-3); these mutations seem to be extremely rare. [15][16][17]22 Our observations demonstrate that individuals carrying germline SDHB and SDHD mutations have some features in common. For example, mean age at diagnosis was 29 years for both genes.…”

Section: Commentmentioning

confidence: 98%

Distinct Clinical Features of Paraganglioma Syndromes Associated With <EMPH TYPE="ITAL">SDHB</EMPH> and <EMPH TYPE="ITAL">SDHD</EMPH> Gene Mutations

Neumann

Pawlu

Pęczkowska³

et al. 2004

JAMA

838

828

View full text Add to dashboard Cite

HEOCHROMOCYTOMA AND PARAganglioma are tumors of the autonomic nervous system. Terminology in science and clinical practice is divergent. Herein, we use the term pheochromocytoma for location in the adrenal glands, extraadrenal abdominal, and thoracic locations (eg, where nearly all tumors are endocrinologically active). In contrast, the term paraganglioma is only used for tumors in the head and neck area where most tumors are nonfunctioning. All these tumors have been described as sporadic and as hereditary entities. [1][2][3] Estimated yearly incidence of

show abstract

“…Somatic mutations in the six known pheochromocytoma/paraganglioma susceptibility genes occur at relatively low incidence (10-25%) in sporadic tumors [5,7]. Candidate gene approaches have identified tumor suppressor genes inactivated in pheochromocytomas, such as the RASassociation domain family 1, isoform A (RASSF1A), and the p16 tumor suppressor genes.…”

Section: Discussionmentioning

confidence: 98%

Human pheochromocytomas show reduced p27Kip1 expression that is not associated with somatic gene mutations and rarely with deletions

Pellegata

Quintanilla-Martı́nez

Keller

et al. 2007

Virchows Arch

View full text Add to dashboard Cite

Pheochromocytomas are neuroendocrine tumors arising in the neural crest-derived chromaffin cells of the adrenal gland or in extra-adrenal sympathetic ganglia (paragangliomas). In a rat model of multiple endocrine neoplasia (MEN), absence of functional p27Kip1 protein predisposes to pheochromocytoma and paraganglioma development. As no data is available regarding the involvement of p27Kip1 in human pheochromocytoma and/or paraganglioma, we set out to determine the expression pattern of p27Kip1 in those tumor types. A panel of 25 pheochromocytomas and 23 paragangliomas was collected. Two pheochromocytomas were from MEN2 patients. The paragangliomas included 15 tumors that developed at the carotid bifurcation, three in the jugulo-tympanic area, and five at other sites. Except for the MEN2 cases, all others were apparently sporadic. Immunohistochemistry for p27Kip1 and the proliferation marker Ki67 was performed. We found that p27Kip1 expression is reduced/lost in 56% of pheochromocytomas, but only in 18.1% of paragangliomas. Downregulation of p27Kip1 was not associated with increased proliferation. Cases showing reduced/lost p27Kip1 expression were screened for the presence of somatic mutations in CDKN1B (p27Kip1) and for allelic imbalance at the p27Kip1 locus. Three cases had allelic imbalance but none had mutations. In conclusion, pheochromocytomas display extreme reduction/loss of p27Kip1 expression at high frequency.

show abstract

Hereditary phaeochromocytomas and paragangliomas: a study of five susceptibility genes

Cited by 64 publications

References 20 publications

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

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

Distinct Clinical Features of Paraganglioma Syndromes Associated With <EMPH TYPE="ITAL">SDHB</EMPH> and <EMPH TYPE="ITAL">SDHD</EMPH> Gene Mutations

Human pheochromocytomas show reduced p27Kip1 expression that is not associated with somatic gene mutations and rarely with deletions

Contact Info

Product

Resources

About