Translocations involving the short arm of chromosome 17 in chronic B-lymphoid disorders: frequent occurrence of dicentric rearrangements and possible association with adverse outcome

Leukemia. 1999 Mar;13(3):460-8. doi: 10.1038/sj.leu.2401272.

Abstract

Unbalanced translocations involving chromosome arm 17p, where the TP53 tumor suppressor gene localizes, are rarely described in chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), but recent use of molecular cytogenetic techniques have indicated a significant incidence of TP53 deletions, suggesting the involvement of chromosome 17p in these disorders. By conventional karyotype, we have identified unbalanced translocations involving 17p in 14 out of 123 (11%) CLL/SLL patients with clonal abnormalities. Cases were characterized by resistance to chemotherapy and a poor clinical outcome. The karyotypes presented a high incidence of complex rearrangements and 17p translocations were characterized by various partners. In 10 cases a centric fusion was assessed by fluorescent in situ hybridization (FISH) experiments using specific centromeric probes. The incidence of dicentric translocations in these series is therefore significantly higher than usually described, arising in up to 71% (10 out of 14 cases). In all cases, translocations led to a monosomy 17p and to a TP53 monoallelic deletion. The adverse clinical outcome confirms that structural abnormalities involving chromosome 17p are associated with disease progression in patients with chronic lymphoproliferative disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Chromosomes, Human, Pair 17*
  • Chronic Disease
  • Cosmids
  • DNA Probes
  • DNA, Satellite / genetics
  • Disease-Free Survival
  • Genes, p53
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Lymphoma, B-Cell / drug therapy
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / pathology
  • Translocation, Genetic*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • DNA Probes
  • DNA, Satellite