Loss of heterozygosity of the MEN1 gene in a large series of TSH-secretingpituitary adenomas

Thyrotropin-secreting pituitary adenomas (TSH-omas) are rare tumors (0.5% o f all pituitary adenomas) showing an invasive behavior and usually sporadic , although a few cases are associated with multiple endocrine neoplasia typ e 1 (MEN1), an autosomal dominant inherited syndrome. This disorder is link ed to loss of heterozygosity (LOH) on 11q13 and inactivating mutations of M EN1 gene, which is located in the same chromosomal region. As other types o f anterior pituitary adenomas, TSH-omas are the result of a monoclonal outg rowth where the intrinsic genetic defects involving oncogenes or tumor supp ressor genes occur in a progenitor cell. However, so far no activating muta tions of particular oncogenes or inactivating mutations of tumor suppressor genes have been identified. Starting from the observation that 3-30% of sp oradic pituitary adenomas show LOH on 11q13, and that allelic losses on the long arms of chromosome 11, beside 10 and 13, are significantly associated with the transition from the non-invasive to the invasive phenotype, we de cided to investigate LOH on 11q13 and mutations of menin in a large series of TSH-omas. Thirteen tumors were evaluated. DNA was extracted from tumors by standard methods and genomic DNA from peripheral blood leukocytes was us ed as control. LOH was screened by using 3 polymorphic markers on 11q13: D1 1S956, PYGM, INT-2. In 3 out of 15 cases we could demonstrate LOH on 11q13, but none of the tumors showed menin mutation after sequence analysis. Thes e data strongly suggest that menin does not play a causative role in the de velopment of TSH-omas, and are in agreement with other studies demonstratin g a limited role of menin in pituitary sporadic tumorigenesis. (C) 2001, Ed itrice Kurtis.