Follicular lymphoma with a novel t(14;18) breakpoint involving the immunoglobulin heavy chain switch mu region indicates an origin from germinal center B cells.
With the use of DNA-fiber fluorescent in situ hybridization, a BCL2 protein positive follicular lymphoma with a novel BCL2 breakpoint involving the immunoglobulin heavy chain (IGH) switch mu (S(mu)) region instead of the J(H) or D(H) gene segments was identified. Sequence analysis showed that the genomic breakpoint is localized between the S(mu) region of the IGH complex and the first intron of BCL2. Reverse-transcriptase polymerase chain reaction showed expression of a unique hybrid IGH-BCL2 transcript involving the transcription initiation site I(mu). Sequence analysis of the V(H) region of the functional nontranslocated IGH allele showed multiple shared somatic mutations but also a high intraclonal variation (53 differences in 15 clones), compatible with the lymphoma cells staying in or re-entering the germinal center. This is the first example of a t(14;18) translocation that results from an illegitimate IGH class-switch recombination during the germinal center B-cell stage.
Fenton
James A L
JA
Department of Pathology, Leiden University Medical Center, The Netherland.
Vaandrager
Jan-Willem
JW
Aarts
Wilhelmina M
WM
Bende
Richard J
RJ
Heering
Karel
K
van Dijk
Martin
M
Morgan
Gareth
G
van Noesel
Carel J M
CJ
Schuuring
Ed
E
Kluin
Philip M
PM
D000368:Aged; D001402:B-Lymphocytes / Q000648:ultrastructure*; D001483:Base Sequence; D002454:Cell Differentiation; D019457:Chromosome Breakage / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics / Q000648:ultrastructure*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics / Q000648:ultrastructure*; D004273:DNA, Neoplasm / Q000235:genetics; D054278:Embryonal Carcinoma Stem Cells; D005260:Female; D005803:Genes, Immunoglobulin; D005812:Genes, Switch; D019254:Genes, bcl-2; D018858:Germinal Center / Q000473:pathology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000648:ultrastructure*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027041:Somatic Hypermutation, Immunoglobulin; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D012334:RNA, Neoplasm