P53 MUTATIONS, C-MYC AND BCL-2 REARRANGEMENTS IN HUMAN NON-HODGKINS-LYMPHOMA CELL-LINES

Fourteen Non-Hodgkin's lymphoma cell lines were generated and assessed for the presence of structural p53, c-myc and bcl-2 gene changes. Sin gle or multiple changes were observed in 11 of the lines. Alterations of the p53 gene were most frequent and documented for 10 lines by immu noprecipition using the antibodies PAb 240 and PAb 1801, sequencing st udies and Southern blot analysis. A detailed study was performed in on e of the cell lines (OCI-Ly4) for which material of the original tumor sample was available. Two point mutations identified by sequencing cD NA derived from the cell line were also present in the original tumor specimen. In contrast, DNA prepared from fibroblasts of the same patie nt did not show the mutations. Six of the 14 lines demonstrated c-myc rearrangements, while bcl-2 changes were observed in 4. The presence o f c-myc was associated with shorter survival of this group of patients with aggressive disease. None of the other changes present as single or composite alterations were correlated with clinical outcome measure s.