The MITF, p.E318K Variant, as a Risk Factor for Pheochromocytoma and Paraganglioma.
Article Details
- CitationCopy to clipboard
Castro-Vega LJ, Kiando SR, Burnichon N, Buffet A, Amar L, Simian C, Berdelou A, Galan P, Schlumberger M, Bouatia-Naji N, Favier J, Bressac-de Paillerets B, Gimenez-Roqueplo AP
The MITF, p.E318K Variant, as a Risk Factor for Pheochromocytoma and Paraganglioma.
J Clin Endocrinol Metab. 2016 Dec;101(12):4764-4768. doi: 10.1210/jc.2016-2103. Epub 2016 Sep 28.
- PubMed ID
- 27680874 [ View in PubMed]
- 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 AND METHODS: Genomic DNA from 555 unrelated patients with PCC/PGL was genotyped for the p.E318K variant in MITF using Sanger sequencing. MAIN OUTCOME MEASURE: 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.