CD44 EXPRESSION IS ABERRANT IN BENIGN SCHWANN-CELL TUMORS POSSESSING MUTATIONS IN THE NEUROFIBROMATOSIS TYPE-2, BUT NOT TYPE-1, GENE

Atypical expression of CD44 splice variants has been implicated in the progression of numerous tumors. This abnormal CD44 expression is pres umed to result from gene alterations that cause tumorigenic transforma tion. Two tumor types that have been linked to specific gene alteratio ns are schwannomas, which have mutations in the neurofibromatosis (NF) type 2 (NF2) gene, and neurofibromas, which characteristically posses s NP type I (NF1) gene mutations. We examined CD44 expression in norma l sciatic nerves, in schwannomas with confirmed NF2 mutations, and in neurofibromas and malignant peripheral nerve sheath tumor tissue and c ell lines from NF1 patients. Compared to normal nerves, schwannomas ex press higher total levels of CD44 and additional splice variants, wher eas CD44 expression in neurofibromas is unaltered. Malignant periphera l nerve sheath tumor tissue and cell lines express the CD44v6 epitope, which is not expressed by normal Schwann cells or by other Schwann ce ll 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 c ells.