410 Background: TGCT is a prototype stem-cell malignancy recapitulating the ontogeny of solid tumors. We studied the roles of differentiation versus dedifferentiation in a bona fide well-differentiated tumor, namely mature teratomas, associated with or without somatic transformation. Methods: Between 2001 and 2013, we identified 7 out of 13 cases in which teratoma and somatic transformation were present within the same residual tumor after chemotherapy and resected at our institution with sufficient quantity and quality for DNA and RNA analysis. We performed primary cell culture, flow cytometry, and xenografts to evaluate stem-ness biomarkers and tumor phenotypes of freshly resected mature teratomas. Results: We detected very few mutations within a preselected gene pool (T200) in all tumor samples. The "within patient mutation agreement" from a mutation matrix of 57 genes, in which at least one mutation occurred between teratoma and somatic transformation, was 86.2 to 94.8%. There was disparity in gene expression, including miR7-3HG, ARHGEF35, and DLX6, between the 7 matched tumor pairs (log2 fold change of about 2). Prospective primary cell culture studies using cell surface stem-ness markers (SSEA3, TRA1-60, Cripto-1, CD90, CD133, CD44) indicate presence of stem cells embedded within residual mature teratomas (n = 3) after chemotherapy. Conclusions: Molecular profiling confirms a common clonal origin between teratoma and somatic transformation but refutes the idea of dedifferentiation of teratoma to somatic transformation. Presence of stem cells embedded within mature teratomas and capable of differentiation into separate ontogenetic lineages could account for the origin of somatic transformation in TGCT.[Table: see text]
349P The amount of cancer stem cells and the sensitivity to anticancer drugs in glioblastoma primary cell culture
