Lack of somatic hypermutation of IG V(H) genes in lymphoid malignancies with t(2;14)(p13;q32) translocation involving the BCL11A gene

Leukemia. 2002 May;16(5):937-9. doi: 10.1038/sj.leu.2402480.

Abstract

The t(2;14)(p13;q32.3) involving the BCL11A and IGH genes is a rare but recurrent chromosomal aberration in B-cell malignancies. Hitherto, juxtaposition of BCL11A and IGH has only been described in B-cell chronic lymphocytic leukemia (B-CLL) and immunocytoma. As subgroups of B-CLL can be distinguished by the pattern of somatic mutation of immunoglobulin variable (V) genes we investigated four lymphomas with IGH/BCL11A involvement for IGH hypermutation. Clonal V(H) gene rearrangements were amplified; in all four cases, sequencing of the amplificates revealed the rearranged V(H) genes to lack somatic mutations. These results suggest that t(2;14)(p13;q32.3) is associated with a subset of B-CLL/immunocytoma characterized by non-mutated IG genes deriving from pre-germinal center B cells. As the translocations in both informative cases are targeted to the switch regions of the IGG2 gene, which is mainly used in T cell-independent immune responses, these translocations presumably occurred in activated B cells in the course of T cell-independent immune responses outside the germinal center.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carrier Proteins*
  • Chromosomes, Human, Pair 14*
  • Chromosomes, Human, Pair 2*
  • Genes, Immunoglobulin
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Switch Region
  • Immunoglobulin Variable Region / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / classification
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Lymphoma, B-Cell / diagnosis
  • Lymphoma, B-Cell / genetics*
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Nuclear Proteins*
  • Repressor Proteins
  • Sequence Analysis, DNA
  • Translocation, Genetic*

Substances

  • BCL11A protein, human
  • Carrier Proteins
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Neoplasm Proteins
  • Nuclear Proteins
  • Repressor Proteins