t(14;18) chromosomal translocation in follicular lymphoma: an event occurring with almost equal frequency both at the D to J(H) and at later stages in the rearrangement process of the immunoglobulin heavy chain gene locus.
bcl-2/IgH fusion is considered a genetic error which occurs at the diversity (D) to joining (J(H)) stage of the gene rearrangement process in the immunoglobulin heavy chain (IgH) gene locus. Translocations of the bcl-2 protooncogene to the IgH locus at ontogenetically later IgH gene rearrangements are thought to represent exceptions. In the present study we analysed the junctional nucleotide sequence of 18 bcl-2/IgH fusion genes identifiable by polymerase chain reaction performed on DNA extracted from diagnostic lymph node tissue of 14 follicular lymphoma patients. In all clones studied, segments of variable length were found interposed between bcl-2 and J(H) gene sequences. Nucleotide sequence data analysis and comparisons performed with the corresponding germline sequences using the GenBank/EMBL database revealed the presence of D segments in most of the bcl-2/IgH fusion genes under study (13/18). By the same kind of computer-aided analysis, previously unrecognized D segments were identified in many published junctional sequences. These results suggest that bcl-2/IgH fusion events are very prevalent in rather more differentiated stages in B-cell ontogeny than previously recognized.
Stamatopoulos
K
K
First Department of Medicine, University of Athens School of Medicine, Laikon General Hospital, Greece.
Kosmas
C
C
Belessi
C
C
Papadaki
T
T
Afendaki
S
S
Anagnostou
D
D
Loukopoulos
D
D
D001483:Base Sequence; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D005784:Gene Amplification; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D019254:Genes, bcl-2 / Q000235:genetics; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic