Dissociation of suppression of tumorigenicity and differentiation in vitro effected by transfer of single human chromosomes into human neuroblastoma cells.

The development of human neuroblastoma is associated with abnormalities of the short arm of chromosome 1 (1p). To determine the importance of sequences on that part of chromosome 1, we transferred translocated chromosomes containing normal portions of chromosome 1p or 1q into the neuroblastoma cell line NGP.1A.TR1 and also normal intact chromosomes 11 and 17 as putative controls. Transfer of chromosome t(X;1q) had no effect on any property we studied of the neuroblastoma cells. It was found that the transfer of chromosome t(X;1p) induced neuronal differentiation, but most of those cells died. The cell lines that grew out from the survivors lacked the t(X;1p) chromosome and were still tumorigenic. Transfer of chromosome 11 induced differentiation but did not affect cell proliferation or the tumorigenic phenotype. We have also demonstrated the existence of a new tumor suppressor gene on chromosome 17 that does not induce differentiation in vitro but completely suppresses the tumor-forming ability of the neuroblastoma cells. Differentiation of neuroblastoma cells in vitro and suppression of tumorigenicity are therefore controlled by multiple genes on different chromosomes and are not necessarily correlated.