Bcl-2/JH rearrangements in benign lymphoid tissues with follicular hyperplasia.
The t(14; 18)(q32;q21) chromosomal translocation, characteristic of follicular lymphoma, couples the bcl-2 protooncogene on chromosome 18 to the immunoglobulin heavy-chain joining region (JH). This results in a deregulated transcription rate of bcl-2, suggesting a major role of the t(14;18) translocation in lymphomagenesis. By using a sensitive polymerase chain reaction technique specific for the major breakpoint region t(14;18), we now demonstrate the presence of bcl-2/JH rearrangements in lymph nodes and tonsils with follicular hyperplasia in 13 of 24 cases (54%). The approximate frequency was one translocation-positive cell in 10(5) cells. No bcl-2/JH rearrangements were detected in reactive lymph nodes without follicular hyperplasia or in bone marrow cells. Sequence analysis showed the amplified bcl-2/JH fragments to be unique to each individual sample and distinct from 24 sequenced follicular lymphoma-derived t(14;18) junctions, thus excluding contamination artifacts. The presence of random nucleotide insertions at the breakpoint junctions suggests a pre-B-cell origin of the t(14;18) translocation, in analogy with follicular lymphomas. We conclude that the t(14;18) translocation can occur in non-malignant tissue and will not, on its own, lead to malignancy.
Limpens
J
J
Department of Pathology, Leiden University, The Netherlands.
de Jong
D
D
van Krieken
J H
JH
Price
C G
CG
Young
B D
BD
van Ommen
G J
GJ
Kluin
P M
PM
D001483:Base Sequence; D001706:Biopsy; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D001854:Bone Marrow Cells; D002460:Cell Line; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D006965:Hyperplasia; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology*; D008206:Lymphatic Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D014066:Palatine Tonsil / Q000276:immunology / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D014069:Tonsillitis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D004247:DNA; D011505:Protein-Tyrosine Kinases