LOSS OF DCC EXPRESSION IN NEUROBLASTOMA IS ASSOCIATED WITH DISEASE DISSEMINATION

DCC, a candidate tumor suppressor gene from chromosome 18q21, is most highly expressed in the developing nervous system. Irt vitro studies s uggest a role for DCC in neuronal differentiation, and 18q allelic los s occurs in a subset of neuroblastomas. To address the hypothesis that loss of DCC function may contribute to tumorigenesis in cells of neur al origin, we utilized a combination of RNase protection, immunoblotti ng, and immunohistochemical approaches to characterize DCC expression in 62 primary neuroblastomas and 16 neuroblastoma cell lines, The DCC protein was undetectable in 38% of the primary tumors and 56% of the c ell lines, Of note, primary tumors lacking DCC expression were more li kely to have been obtained from patients with disseminated or stage D disease (P = 0.01). In addition, loss of DCC expression was observed i n three of six primary tumors from stage DS patients. No consistent re lationship between the loss of DCC expression and N-myc amplification was observed in our studies, Our findings suggest that loss of DCC exp ression may contribute to the dissemination of neuroblastoma cells, pe rhaps through alterations in growth and differentiation pathways disti nct from those regulated by N-myc.