The MITF, p.E318K Variant, as a Risk Factor for Pheochromocytoma and Paraganglioma.
J Clin Endocrinol Metab
; 101(12): 4764-4768, 2016 12.
Article
in En
| MEDLINE
| ID: mdl-27680874
ABSTRACT
CONTEXT The microphthalmia-associated transcription factor (MITF) regulates the survival, proliferation, and differentiation of neural crest-derived lineages. Recent studies reported an increased risk of melanoma in individuals carrying the rare variant MITF, p.E318K (rs149617956). Whether this variant plays a role in other neural crest-derived tumors is unknown. OBJECTIVE:
In the present study, we aimed at determining the prevalence of the MITF, p.E318K variant, in a well-characterized French cohort of pheochromocytomas/paragangliomas (PCC/PGL). DESIGN ANDMETHODS:
Genomic DNA from 555 unrelated patients with PCC/PGL was genotyped for the p.E318K variant in MITF using Sanger sequencing. MAIN OUTCOMEMEASURE:
The prevalence of the mutation in the PCC/PGL cohort was compared with a population-based sample of 2348 ethnically matched controls.RESULTS:
We identified seven carriers (five patients with sporadic PCCs, two with PGLs). The prevalence of the MITF, p.E318K variant, was higher in the PCC/PGL cohort than in controls, and appears to be a significant risk factor (odds ratio, 3.19; 95% confidence interval, 1.34-7.59; P = .005). Noteworthy, two patients were homozygous for the p.E318K risk allele, a patient with metastatic PCC and an SDHB-mutated patient with PGL.CONCLUSION:
Our results indicate that the germline variant MITF, p.E318K is associated with an increased risk of other neural crest-derived tumors such as PCC/PGL.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Paraganglioma
/
Adrenal Gland Neoplasms
/
Microphthalmia-Associated Transcription Factor
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Journal:
J Clin Endocrinol Metab
Year:
2016
Document type:
Article
Affiliation country:
France