Two malignant peripheral primitive neuroepithelial tumor cell lines established from consecutive samples of one patient: Characterization and cytogenetic analysis

Abstract

A 6-year-old girl presented with a tumor of the right shoulder involving bone, adjacent soft tissue, and regional lymph nodes. The conventional histologic diagnosis was ambiguous, initially suggesting lymphoma. After relapse on lymphoma therapy, reevaluation with additional multiple diagnostic techniques performed on the biopsy tissue and on two cell lines derived from the biopsies established the diagnosis of a primitive neuroepithelial tumor of bone and soft tissue. This was strongly supported by 1) focal rosette formation by the tumor cells and positive immunostaining for neuron-specific enolase and synaptophysin, with absent staining for leukocyte common antigen; 2) at the ultrastructural level, formation of cellular processes containing microtubules, a paucity of neurosecretory granules, absence of synaptic junctions, formation of long "intermediate" junctions between cells, and, in culture, widespread development of rosettes; 3) marked surface positivity to W 6/32 and negativity to HSAN 1.2 antibodies; and 4) elevated expression of MYC and lack of overexpression of MYCN oncogenes. Numerical and structural abnormalities were present in the karyotype, but the expected t(11;22)(q24;q12) was not present in the tumor-involved marrow or in either of the established tumor cell lines, although there was an interstitial deletion of 11q involving breakpoints in q21 and q23.

Cancer Cell Lines as Genetic Models of Their Parent Histology: Analyses Based on Array Comparative Genomic Hybridization

“…Although genome-wide RNA profiles of cancer cell lines have often been used in recent years to model drug response and other characteristics in vitro (42), it may be advantageous to conduct these investigations with DNA-based profiles or with combined DNA/RNA profiles. First, although careful in vitro modeling of oncogenic activation can dissect RNA profiles that correlate with drug response and may correlate with in vivo tumor profiles (43), the relationship between cell lines used for in vitro studies and their fresh-frozen tissue counterparts is often questionable (16)(17)(18). In addition, it is unknown whether successful transcriptional meta-profiles (33) could be independently calculated by exclusively using cell lines.…”

“…In addition, multiple growth passages, to which commercially available cell lines are routinely subjected, have been shown to be associated with random genomic instability (15). Finally, past studies have noted differences in gene expression patterns between cell lines and their fresh-frozen tissue counterparts (16)(17)(18). Despite these observations, more recent analyses of genetic aberrations from larger panels of cell lines and tumors indicate a close concordance of genetic changes within individual histologies (e.g., breast cancer; ref.…”

Enhanced MYCN expression and lsochromosome 17q in pineoblastoma cell lines

“…Both lines showed strong staining with W6/32; however, neither line stained with HSAN 1.2. This pattern of surface marker expression is characteristic for peripheral P N E T cells and contrasts with the results for neuroblastoma cells (Kees et al, 1992a). T h e RFB-1 antibody which recognizes the product of the MICZ locus (Banting et al, 1989) stained both cell lines, whereas no staining was obtained with 2D1, specific for LCA.…”

“…T h e analysis of surface markers was performed on cells that had been in culture for 4 to 9 months using a panel of monoclonal antibodies (Kees et al, 1992a). T h e two cell lines exhibited similar surface marker profiles (Table 1).…”

Musculoskeletal Oncology:Advances in Cytogenetics and Molecular Genetics and their Clinical Implications

“…Non-random aberrations such as trisomy 8 and translocations involving chromsomes 1 and 16 have also been reported (45). The fact that an identical t(l1;22)(q24;q12) has been observed in neuroepithelioma, Askin tumors and esthesioneuroblastomas (46)(47)(48)(49) (48,50). The EWS/ FLIl chimeric protein has been shown to function as a transcriptional activator (51), and the molecular mechanism for this appears to be the replacement<of the N-terminal transcriptional activation domain of the FLIl protein with the regulatory domain of EWS which results in the activation of the C-terminal transcriptional activation domain of FLI1.…”