Combined characterization of a pituitary adenoma and a subcutaneous lipoma in a MEN1 patient with a whole gene deletion

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder associated with mutations of the MEN1 gene, which is characterized by combined tumors of the parathyroid glands, pancreatic islet cells, and the anterior pituitary. A significant number of patients with the clinical features of MEN1, however, do not show MEN1 mutations upon direct sequencing. We describe a young woman who fulfilled the clinical and biochemical criteria for MEN1 syndrome, but DNA sequencing did not indicate any MEN1 mutations. She developed a prolactin-secreting pituitary macroadenoma, primary hyperparathyroidism with parathyroid hyperplasia, pancreatic lesions, and two subcutaneous lipomas. Array comparative genomic hybridization (aCGH) analysis of peripheral blood DNA revealed a heterozygous germline deletion at 11q13.1 that spanned at least 22.23 kilobases and contained the entire MEN1 gene. Integrated aCGH and cytogenetic analyses of the adenoma and lipoma tissues revealed somatic inactivation of the wild-type MEN1 allele by different routes: the second hit of MEN1 recessive oncogenesis leading to adenoma implied a loss of heterozygosity, whereas a balanced translocation deleting the wild-type MEN1 allele primed the lipoma development. These findings show that aCGH is a valuable means of optimizing genetic testing in MEN1 patients which complements other technologic approaches to elucidating the pathologic mechanisms of MEN1 tumors.