Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma

Peter Leif Bergsagel, Marta Chesi, Elena Nardini, Leslie A. Brents, Suzanne L. Kirby, W. Michael Kuehl

Research output: Contribution to journalArticle

302 Scopus citations

Abstract

In multiple myeloma, karyotypic 14q32 translocations have been identified at a variable frequency (10-60% in different studies). In the majority of cases, the partner chromosome has not been identified (14q+), and in the remaining cases, a diverse array of chromosomal partners has been implicated, with 11q13 being the most common. We developed a comprehensive Southern blot assay to identify and distinguish different kinds of immunoglobulin heavy chain (IgH) switch recombination events. Illegitimate switch recombination fragments (defined as containing sequences from only one switch region) are potential markers of translocation events into IgH switch regions and were identified in 15 of 21 myeloma cell lines, including seven of eight karyotyped lines that have no detectable 14q32 translocation. From all nine lines or tumor samples analyzed further, cloned illegitimate switch recombination fragments were confirmed to be IgH switch translocation breakpoints. In three of these cases, the translocation breakpoint was shown to be present in the primary tumor. These translocation breakpoints involve six chromosomal loci: 4p16.3 (two lines and the one tumor); 6; 8q24.13; 11q13.3 (in three lines); 16q23.1; and 21q22.1. We suggest that translocations into the IgH locus (i) are frequent (karyotypic 14q32 translocations and/or illegitimate switch recombination fragments are present in primary tumor samples and in 19 of 21 lines that we have analyzed); (ii) occur mainly in switch regions; and (iii) involve a diverse but nonrandom array (i.e., frequently 11q13 or 4p16) of chromosomal partners. This appears to be the most frequent genetic abnormality in multiple myeloma.

Original languageEnglish (US)
Pages (from-to)13931-13936
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number24
DOIs
StatePublished - Nov 26 1996
Externally publishedYes

    Fingerprint

Keywords

  • chromosome translocation
  • cyclin D1
  • immunoglobulin heavy chain gene
  • isotype switch recombination

ASJC Scopus subject areas

  • Genetics
  • General

Cite this