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The MITF, p.E318K Variant, as a Risk Factor for Pheochromocytoma and Paraganglioma

Luis Jaime Castro-Vega1, Soto Romuald Kiando1, Nelly Burnichon1

  • 1INSERM (L.J.C.-V., S.R.K., N.K., A.B., L.A., N.B.-N., J.F., A.-P.G.-R.), UMR970, Paris-Cardiovascular Research Center, F-75015, Paris, France; Université Paris Descartes (L.J.C.-V., S.R.K., N.B., A.B., L.A., N.B.-N., J.F., A.-P.G.-R.), PRES Sorbonne Paris Cité, Faculté de Médecine, F-75006 Paris, France; Service de Génétique, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (N.B., C.S., A.-P.G.-R.), F-75015, Paris, France; Unité Hypertension artérielle (L.A.), Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, F-75015, Paris, France; Département de Cancérologie endocrinienne and Université Paris-Saclay (A.B., M.S.), Gustave Roussy, Villejuif, F-94805, France; Université Paris 13 (P.G.), Equipe de Recherche en Epidémiologie Nutritionnelle (EREN), Centre d'Epidémiologie et Statistiques Sorbonne Paris Cité, INSERM (U1153), Inra (U1125), Cnam, COMUE Sorbonne Paris Cité, Bobigny; INSERM (B.B.-d.P.), U1186, Université Paris-Sud, Université Paris-Saclay, Villejuif, F-94805, France; Département de Biopathologie (B.B.-d.P.), Gustave Roussy, Villejuif, F-94805, France; and Rare Adrenal Cancer Network COMETE (L.A., A.-P.G.-R.), F-75006, Paris, France.

The Journal of Clinical Endocrinology and Metabolism
|September 30, 2016
PubMed
Abstract

Insights

The rare microphthalmia-associated transcription factor (MITF) p.E318K variant increases the risk of pheochromocytomas/paragangliomas (PCC/PGL). This finding suggests MITF variants may contribute to other neural crest-derived tumors.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • The microphthalmia-associated transcription factor (MITF) is crucial for neural crest cell development.
  • A rare variant, MITF p.E318K, is linked to increased melanoma risk.
  • The role of MITF p.E318K in other neural crest-derived tumors remains unexplored.

Purpose of the Study:

  • To investigate the prevalence of the MITF p.E318K variant in a French cohort of pheochromocytomas/paragangliomas (PCC/PGL).
  • To determine if the MITF p.E318K variant is a risk factor for PCC/PGL development.

Main Methods:

  • Genotyping of the MITF p.E318K variant using Sanger sequencing in 555 unrelated PCC/PGL patients.
  • Comparison of variant prevalence in the patient cohort with 2348 ethnically matched controls.

Main Results:

  • The MITF p.E318K variant was identified in seven PCC/PGL patients (five sporadic PCCs, two PGLs).
  • Variant prevalence was significantly higher in the PCC/PGL cohort than in controls (OR, 3.19; P = .005).
  • Two homozygous carriers were identified, including one with metastatic PCC and one with PGL.

Conclusions:

  • The germline MITF p.E318K variant is associated with an elevated risk of developing PCC/PGL.
  • This suggests MITF p.E318K may be a risk factor for a broader range of neural crest-derived tumors.

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