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IGH switch breakpoints in Burkitt lymphoma: Exclusive involvement of noncanonical class switch recombination
Author(s) -
Guikema Jeroen E. J.,
de Boer Conny,
Haralambieva Eugenia,
Smit Laura A.,
van Noesel Carel J. M.,
Schuuring Ed,
Kluin Philip M.
Publication year - 2006
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20345
Subject(s) - breakpoint , immunoglobulin class switching , biology , chromosomal translocation , southern blot , genetics , microbiology and biotechnology , immunoglobulin heavy chain , gene rearrangement , recombination , gene , antibody , b cell
Most chromosomal t(8;14) translocations in sporadic Burkitt lymphomas (BL) are mediated by immunoglobulin class switch recombination (CSR), yet all tumors express IgM, suggesting an incomplete or exclusively monoallelic CSR event. We studied the exact configuration of both the nontranslocated IGH allele and the MYC/IGH breakpoint by applying a combination of low‐ and high‐resolution methods (interphase FISH, DNA fiber FISH, long‐distance PCR, and Southern blotting) on 16 BL. IGH class switch events involving the nontranslocated IGH allele were not observed. Thirteen cases had MYC/IGH breakpoints in or nearby IGH switch (S) sites, including five at Sμ, three at Sγ and five at Sα. All eight translocations with a breakpoint at Sγ or Sα were perfectly reciprocal, without deletion of Cμ‐Cδ or other CH elements. Internal Sμ deletions claimed to be a marker for CSR activity and implicated in stabilization of IgM expression were found in BL but did not correlate with downstream translocation events. This study shows that switch breakpoints in sporadic BL are exclusively resolved by a noncanonical recombination mechanism involving only one switch region. © 2006 Wiley‐Liss, Inc.