Clonal origin of pituitary adenomas. Benign pituitary adenomas are among the most common neurosurgical tumors and account for a diversity of clinical syndromes due to their hormone content and release. To determine whether these tumors arise from a single cell or multiple cells, the authors studied X chromosome inactivation in deoxyribonucleic acid (DNA) isolated from pituitary adenomas in women. Tumors of three different hormonal subtypes were examined. One tumor contained cells immunoreactive for prolactin and human growth hormone; one tumor contained foci immunoreactive for the beta-subunits of luteinizing hormone and follicle-stimulating hormone; and the third tumor had no immunoreactive prolactin, human growth hormone, beta-subunits of thyroid-stimulating hormone, luteinizing hormone, or follicle-stimulating hormone, or the alpha-subunit. Analysis of the DNA revealed that, in each of the three pituitary tumors, one X chromosome was active in all cells and one X chromosome was inactive, indicating that each of these tumors was monoclonal in origin. It is concluded that clinically evident pituitary tumors arise from a genetic mutation in a single cell. 