CHARACTERIZATION OF A PRIMARY CENTRAL-NERVOUS-SYSTEM ATYPICAL TERATOID RHABDOID TUMOR AND DERIVATIVE CELL-LINE - IMMUNOPHENOTYPE AND NEOPLASTIC PROPERTIES/

Primary central nervous system (CNS) atypical teratoid/malignant rhabd oid tumors (ATT/RhT) occur during early childhood and are almost invar iably fatal. Expression of multiple phenotypes in ATT/RhT suggests the presence of an undifferentiated progenitor with the potential to diff erentiate along multiple lines. These properties have made it difficul t to characterize the etiology and histogenesis of these tumors and co mplicate efforts to develop targeted therapies. This paper characteriz es the immunophenotype of a human CNS ATT/RhT and describes the proper ties of a derivative cell line (Atrt95) which retained morphological a nd immunochemical characteristics of the parent tumor including divers e differentiation. Most tumor cells were strongly immunoreactive for g lial fibrillary acidic protein, vimentin and A2B5. Scattered, large tu mor cells that showed a rhabdoid phenotype were immunoreactive for syn aptophysin. The morphology of cultured Atrt95 cells was heterogeneous, but often fit into 1 of 3 classes that appeared to correspond to cell populations observed within the parent tumor including: 1) tightly-pa cked small-cell colonies, 2) large, well-spread highly motile cells an d 3) arrays of elongated cells. In vitro assays demonstrated that grow th of the entire culture was anchorage-dependent but not serum-depende nt. Transplantation of Atrt95 cells into the rat spinal cord resulted in tumor growth and CNS invasion. Preliminary cytogenetics study revea led complex aneuploidy but no apparent monosomy or deletions of chromo some 22. The immunophenotype of this neoplasm and derivative cell line is consistent with a primitive glioneuronal lineage and its in vitro characteristics are that of an invasive malignancy similar to the natu rally occurring tumor. This unique cell line (Atrt95) provides a valua ble model to study the biology and genetics of the CNS ATT/RhT.