The absence of ongoing immunoglobulin gene hypermutation suggests a distinct mechanism for c-myc mutation in endemic Burkitt's lymphoma.
OBJECTIVE
Burkitt's lymphoma is a malignancy of mature, immunoglobulin (Ig)-bearing B cells characterized by translocation between c-myc and Ig gene loci. A role for the juxtaposed Ig genes in the mutation and deregulation of c-myc expression typical of endemic Burkitt's lymphoma (eBL) has been proposed, but never proven. Our objective was to determine whether Ig gene hypermutation is ongoing in eBL.


METHODS
We isolated Ig heavy-chain sequences from K962 eBL tumor cells using reverse transcription and polymerase chain reaction (PCR) amplification. The PCR product was ligated into Bluescript II vectors. Multiple subclones were sequenced and the variable regions were compared for evidence of ongoing Ig hypermutation.


RESULTS
Six total single base substitutions were observed within four of the nine subclones studied. Four substitutions resulted in amino acid changes and two were silent. There was no clustering of mutations in hypervariable regions, or a high incidence of amino acid replacement or link substitutions, all of which are characteristic of Ig hypermutation. The observed mutations occurred at a rate consistent with Taq polymerase error.


CONCLUSIONS
Our data indicate that in the eBL tumor sample K962, the mechanism underlying c-myc mutation is distinct from that which gives rise to Ig hypermutation.
Cowley
C G
CG
Department of Pediatrics, University of Utah, Salt Lake City 84112, USA.
Carroll
W L
WL
Johnston
J M
JM
D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D004252:DNA Mutational Analysis; D004259:DNA-Directed DNA Polymerase; D005803:Genes, Immunoglobulin / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D019914:Taq Polymerase; D014407:Tumor Cells, Cultured
D012334:RNA, Neoplasm; D019914:Taq Polymerase; D012194:RNA-Directed DNA Polymerase; D004259:DNA-Directed DNA Polymerase