Molecular cytogenetic analysis of genomic instability at the 1q12-22 chromosomal site in B-cell non-Hodgkin lymphoma

Genes Chromosomes Cancer. 2002 Dec;35(4):318-28. doi: 10.1002/gcc.10120.

Abstract

Abnormalities of chromosome arm 1q have frequently been reported in B-cell non-Hodgkin lymphoma (NHL), and correlated with poor outcome. Five genes mapped to this region (BCL9, MUC1, FCGR2B, IRTA1, and RTA2) have been shown to be deregulated by juxtaposition with the IG genes. However, abnormalities of the 1q21-22 region that are not involved in translocations with the IG genes have not been addressed. We performed a molecular cytogenetic analysis of 1q12-22 abnormalities in 24 B-cell NHL cases. The cases analyzed were in two groups: one, composed of 18 cases with the single break in the 1q12-22 region, and another, composed of six cases with multiple breaks in the 1q12-22 region. The involvement of heterochromatin and its vicinity was observed most frequently in the single-break cases (13 of 18 cases). In this group, the recurring partner region was 1q32, which resulted in dup(1)(q12-21q32) or trp(1)(q12q32) in 5 cases. The 6 cases with multiple breaks showed an unexpected level of instability along with complex combinations of abnormalities, especially sequential duplication and inversion, in the 1q12-22 region. The BCL9 locus was deleted by complex aberration in 2 of 6 cases. High-level amplification of the WI-16757 locus was found in 2 cases. Our studies demonstrate a high level of instability of the 1q12-22 region, possibly stemming from its chromatin organization. Chromosome arm 1q is gene-rich, and characterization of aberrations described in this study can be expected to lead to the discovery of additional functionally significant genetic changes.

Publication types

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

MeSH terms

  • Chromosome Aberrations*
  • Chromosome Breakage / genetics
  • Chromosome Deletion
  • Chromosome Inversion
  • Chromosome Mapping / methods*
  • Chromosome Painting / methods
  • Chromosomes, Human, Pair 1 / genetics*
  • Cohort Studies
  • Cytogenetic Analysis / methods*
  • Female
  • Genetic Markers / genetics
  • Heterochromatin / genetics
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • Lymphoma, B-Cell / genetics*
  • Male
  • Neoplasm Proteins / genetics
  • Prospective Studies
  • Transcription Factors
  • Translocation, Genetic / genetics

Substances

  • BCL9 protein, human
  • Genetic Markers
  • Heterochromatin
  • Neoplasm Proteins
  • Transcription Factors