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CD44 Expression Is Aberrant in Benign Schwann Cell Tumors Possessing Mutations in the Neurofibromatosis Type 2, but not Type 1, Gene¹

Forschungszentrum Karlsruhe, Institut für Genetik, 76021 Karlsruhe, Germany [L. S., P. H., H. P.]; Molecular Neurogenetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129 [L. B. J.]; Institut für Neuropathologie, Universitätsspital Zürich, CH-8091 Zürich, Switzerland [J. L., A. A.]; and Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati Medical Center, Cincinnati, Ohio 45267 [P. P.].

Atypical expression of CD44 splice variants has been implicated in the progression of numerous tumors. This abnormal CD44 expression is presumed to result from gene alterations that cause tumorigenic transformation. Two tumor types that have been linked to specific gene alterations are schwannomas, which have mutations in the neurofibromatosis (NF) type 2 (NF2) gene, and neurofibromas, which characteristically possess NF type 1 (NF1) gene mutations. We examined CD44 expression in normal sciatic nerves, in schwannomas with confirmed NF2 mutations, and in neurofibromas and malignant peripheral nerve sheath tumor tissue and cell lines from NF1 patients. Compared to normal nerves, schwannomas express higher total levels of CD44 and additional splice variants, whereas CD44 expression in neurofibromas is unaltered. Malignant peripheral nerve sheath tumor tissue and cell lines express the CD44v6 epitope, which is not expressed by normal Schwann cells or by other Schwann cell tumors. These data indicate that altered CD44 expression correlates strictly with mutations in the NF2 but not NF1 gene and suggest that CD44v6 might be a marker for the malignant transformation of Schwann cells.

¹ This work was supported by Grant He551/8-2 from the Deutsche Forschungsgemeinschaft.

² To whom requests for reprints should be addressed, at Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati Medical Center, 231 Bethesda Ave., Cincinnati, OH 45267.

Received 12/11/96. Accepted 9/ 4/97.

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