Mechanism of bcl-2 activation in human follicular lymphoma.
The t(14; 18) chromosomal translocation of human follicular lymphoma recombines the bcl-2 gene from chromosome 18 with the immunoglobulin heavy chain joining region. In the t(14; 18) translocation bearing cell line SU-DHL-6, this results not only in an inappropriately high rate of bcl-2 transcription for a mature B cell, but also in two potentially critical point mutations. To determine the relative importance of these mutations, we searched for their presence in DNA from the involved lymph nodes of 12 patients with t(14; 18) follicular lymphoma. bcl-2 genomic sequences were specifically amplified by the polymerase chain reaction technique and then directly sequenced. None of the 12 samples analysed revealed the codon 7 or codon 129 mutation detected in SU-DHL-6. We conclude that abnormal expression of bcl-2 rather than structural alterations at codon 7 or 129 play an important role in the disordered growth and differentiation of follicular B-cell lymphoma.
Hua
C
C
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Raffeld
M
M
Ko
H S
HS
Fast
P
P
Bakhshi
A
A
Cossman
J
J
D001402:B-Lymphocytes; D004273:DNA, Neoplasm / Q000032:analysis; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D008223:Lymphoma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051562:Proto-Oncogene Proteins c-bcr; D011519:Proto-Oncogenes; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr