Complex MAX Rearrangement in a Family With Malignant Pheochromocytoma, Renal Oncocytoma, and Erythrocytosis.
J Clin Endocrinol Metab
; 101(2): 453-60, 2016 Feb.
Article
en En
| MEDLINE
| ID: mdl-26670126
ABSTRACT
CONTEXT Familial pheochromocytoma (PCC) has been associated with germline mutations in 16 genes. Here we investigated three siblings presenting with bilateral pheochromocytomas. In addition, the index patient also exhibited renal oncocytoma and erythrocytosis, whereas the second sibling presented with a lymph node metastasis. DESIGN:
First, single-nucleotide polymorphism array and exome sequencing were performed on germline and PCC-derived DNA to identify genomic alterations in the index patient. Second, alterations were confirmed and validated by Sanger sequencing, analyzed by (multiplexed) PCR to determine the loss of the wild-type allele, and investigated by immunohistochemistry in the tumors of the three siblings.RESULTS:
The index patient's germline DNA revealed a large complex genomic alteration encompassing the intragenic and promoter regions of Myc-associated factor X (MAX) and alpha-(1,6)-fucosyltransferase (FUT8). In all three siblings the MAX alteration was confirmed, and the loss of the wild-type MAX and FUT8 alleles was demonstrated in all tumors. Uniparental disomy of chromosome 14q, previously demonstrated as a hallmark for MAX-related PCC, was shown in the index patient's PCC by single-nucleotide polymorphism array. Loss of MAX and FUT8 protein expression was demonstrated by immunohistochemistry in the tumors from the three siblings.CONCLUSIONS:
Our results indicate that large genomic deletions of MAX should be considered in familial and bilateral PCC with prior negative testing for gene mutations. In addition, our results confirm that MAX is a tumor suppressor gene for renal oncocytomas.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Feocromocitoma
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Policitemia
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Neoplasias de las Glándulas Suprarrenales
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Adenoma Oxifílico
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2016
Tipo del documento:
Article