DETECTION OF SOMATIC MUTATIONS OF THE BCL-2 ONCOGENE IN B-CELL LYMPHOMAS WITH THE T(14-18)

The incidence of mutations within the first 582 bp of the open reading frame of the bcl-2 gene, has been investigated in presentation lymph node samples, from 7 cases with follicular non-Hodgkin's lymphoma (NHL ), 1 case with centroblactic NHL, the DOHH, cell line derived from the immunoblastic transformation of a follicular NHL and one case with be nign follicular hyperplasia. A total number of 43 point mutations with in the examined portion of the bcl-2 gene were detected in the cases a nalysed including the DOHH, cell line. Similar analysis of peripheral blood lymphocytes from 2 normal individuals that lacked the t(14;18), revealed no mutations in one case and a single 101 bp A-->G transition in clone, in the other. Missense mutations were detected in 7/8 NHLs, the DOHH2 cell line and the case of benign follicular hyperplasia. Th ere was a significantly higher frequency of mutations within the regio n corresponding to the BH1, one of the two known functional domains, o f the bcl-2 protein. The same position, 445 bp of the bcl-2 gene, was found to be involved in missense mutations affecting the DOHH2 cell li ne and 3 cases with follicular NHL.