Mutations of the MEN1 tumor suppressor gene in sporadic pituitary tumors

Pituitary adenoma is a common neoplasm accounting for 10% of all intracranial tumors. Although the molecular mechanisms underlying the formation of these tumors are largely unknown, a small portion of pituitary adenomas occur in patients with the multiple endocrine neoplasia syndrome type 1 (MEN 1). Although two groups in the United States and Canada have recently reported that sporadic pituitary adenomas very rarely harbor a somatic mutation in the MEN1, MEN1 gene mutation analysis in sporadic pituitary adenomas has not yet been carried out in the Japanese population. To elucidate the potential etiological role of the MEN1 gene in the formation of sporadic pituitary adenomas in Japan, we investigated 40 Japanese patients with sporadic pituitary adenomas (16 hormone-secreting and 24 nonsecreting tumors) for MEN1 gene mutation. Polymerase chain reaction–single-stranded DNA conformation polymorphism analysis and sequencing demonstrated a somatic mutation in the MEN1 gene in only one of the 40 tumors, a prolactinoma, which had a 1-bp deletion in the coding sequence of exon 2. The data suggest that somatic mutations in the MEN1 gene do not play a prominent role in the pathogenesis of sporadic pituitary adenomas.