REDUCED EXPRESSION OF SCHWANNOMIN MERLIN IN HUMAN SPORADIC MENINGIOMAS/

OBJECTIVE: The neurofibromatosis type 2 gene is frequently mutated in sporadic meningiomas. The protein product of the neurofibromatosis typ e 2 gene is called schwannomin or merlin. Its expression in leptomenin geal cells from which meningiomas are derived and the characteristics of mutated forms in meningiomas, to our knowledge, have not been previ ously studied. METHODS: Immunoblotting and immunoprecipitation experim ents with two specific antibodies were used to determine the size and subcellular distribution of schwannomin/merlin in rabbit and human bra in tissue and established human leptomeningeal LTAg2B cells. Immunoblo tting was used to determine the expression level of schwannomin/merlin in 14 human sporadic meningiomas. RESULTS: Both antibodies detect a p rotein of approximately 66 kDa, which is predominantly expressed in th e Triton X-100-insoluble fraction of the brain and LTAg2B cells. The l evels of schwannomin/merlin were severely reduced in eight tumors (57% ) when compared with the expression levels in the human brain, LTAg2B cells, and the remaining six meningiomas. All six tumors with the norm al schwannomin/merlin expression were of meningo-theliomatous type. In contrast, all other histological types and one meningotheliomatous tu mor with psammoma bodies were deficient in the 66-kDa schwannomin/merl in. Although nonsense mutations leading to premature stop codons are c ommon in the neurofibromatosis type 2 gene in meningiomas, we found no evidence of truncated schwannomin/merlin forms in the tumors analyzed . CONCLUSION: The absence of complete schwannomin/merlin in almost 60% of primary sporadic meningiomas seems to be an important factor in me ningioma tumorigenesis. The development of meningotheliomatous meningi omas is probably linked to alterations in other oncogenes or tumor sup pressor genes.