ras mutations in human prolactinomas and pituitary carcinomas

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Abstract
Pituitary adenomas have been shown to be clonal in origin, indicat- ing that one or more somatic mutations underlie tumor pathogenesis. Mutated oncogenic forms of ra.s protein have been identified in a number of human neoplasms, including thyroid adenomas and carci- nomas. However, the potential role of activated ros in the development of specific human pituitary tumor phenotypes has not been determined. Although rus mutations were not found in glycoprotein hormone- secreting or somatotroph adenomas, we recently identified a mutation in the H-ras gene (Gly-Val) at codon 12 in a highly invasive prolacti- noma. These data raise the possibility that ras mutations might play a role in the pathogenesis of PRL-secreting pituitary tumors and/or may be a marker for tumor invasiveness and malignant transformation. Therefore, we investigated 78 pituitary tumors (59 prolactinomas, 13 invasive prolactinomas, and 6 pituitary carcinomas) for activating point mutation in the three ras genes using oligonucleotide-specific hybridi- zation. In contrast to the relatively high frequency of ro.s mutations in many different tumor types, no ras mutations were identified in either prolactinomas or pituitary carcinomas. Our data indicate that ~0s mutations are rare in prolactinomas and pituitary carcinomas. (J Clin Endocrinol Metab 78: 89-93,1994)

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