ALTERED EXPRESSION OF THE RETINOBLASTOMA GENE-PRODUCT IN HUMAN HIGH-GRADE NON-HODGKINS-LYMPHOMAS

The retinoblastoma gene (RB) is a growth suppressor gene on the human chromosome 13q14. It encodes a 105 kDa phosphoprotein (p105), with DNA -binding capacity. P105 is thought to be involved in cell cycle contro l. Inactivation of RB is responsible for the development of retinoblas tomas and occurs frequently in osteosarcomas and small cell lung cance r. In this study we looked at the RB-structure and expression in cell lines and primary lymphoma samples from patients with high grade non-H odgkin's lymphoma (NHL). Forty five primary high grade NHL, the B-lymp hoblastoid eel line IM-9 and the NHL cell line WSU-NHL were studied fo r RB structure by Southern blotting and for RB-expression by Northern blotting, Western blotting and immunocytochemistry. in all experiments freshly cryopreserved material was used. Southern and Northern experi ments were performed with the 0.9 kb and 3.8 kb RB-cDNA probe. For the detection of p105 two different anti-p105-monoclonal antibodies were used in immunocytochemistry and Western blotting experiments. No RB mR NA and no p105 could be found in IM-9 cells. Twenty six high grade NHL samples (58%) showed no p105 expression. In the subgroup of centrobla stic lymphomas 16 out of 21 and in Burkitt's lymphomas five out of eig ht showed no p105 expression. P105 expression is absent in 58% of high grade NHL, particularly in centroblastic and Burkitt's lymphomas, sug gesting that inactivation of RB may play a crucial role in the pathoge nesis of high grade NHL.