Characteristic pattern of chromosomal imbalances in posttransplantation lymphoproliferative disorders: correlation with histopathological subcategories and EBV status

Transplantation. 2005 Jul 27;80(2):176-84. doi: 10.1097/01.tp.0000163288.98419.0d.

Abstract

Background: Posttransplantation lymphoproliferative disorders (PTLDs) are a spectrum of lymphoid proliferations, occurring in immunosuppressed organ transplant recipients. They comprise early lesions, polymorphic (P-PTLD), monomorphic (M-PTLD), and Hodgkin/Hodgkin-like lymphoma PTLD (HL-PTLD) lesions. Most of them are associated with Epstein-Barr virus (EBV). Little is known about their genetic changes.

Materials and methods: We have studied 35 PTLDs[7 P-PTLDs (3/7 polyclonal IgH), 26 M-PTLDs (22 B-cell PTLD, 4 T-cell PTLD), 2 HL-PTLDs], using comparative genomic hybridization (CGH), a DNA-based technique allowing a screening of chromosomal imbalances without needing cultured cells. RESULTS.: Overall incidence of chromosomal imbalances: 51.5 %. The most frequent gains involved 8q24, 3q27 [4 cases each]; 2p24p25, 5p, 9q22q34, 11, 12q22q24, 14q32, 17q, 18q21 [2 cases each]. Nonrandom losses were 17p13 [4 cases]; 1p36, 4q [3 cases each]; 17q23q25, Xp [2 cases each]. Three high-level amplifications were detected: 4p16, 9p22p24, 18q21q23. In this latter imbalance, involvement of Bcl2 has been confirmed by FISH. The nonrandom CGH imbalances occurring in M-PTLD are usually described in lymphomas of immunocompetent patients and contain genes known to be involved in lymphomagenesis, while genomic abnormalities detected in half cases of EBV positive P-PTLD are mostly unknown.

Conclusion: This study reported nonrandom chromosomal imbalances in PTLD and also identified early genomic alterations in EBV positive P-PTLD. These results raise two questions: the role of such lesions in the development and progression of those EBV induced-lymphoproliferations and their clinical significance especially in P-PTLD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • Child, Preschool
  • Chromosomal Instability / genetics*
  • Chromosome Mapping
  • Epstein-Barr Virus Infections / epidemiology
  • Female
  • Gene Rearrangement
  • Genes, Immunoglobulin
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Immunophenotyping
  • Infant
  • Lymphoproliferative Disorders / genetics*
  • Lymphoproliferative Disorders / pathology
  • Lymphoproliferative Disorders / virology
  • Male
  • Middle Aged
  • Organ Transplantation / adverse effects*
  • Postoperative Complications / physiopathology
  • Postoperative Complications / virology
  • Receptors, Antigen, T-Cell / genetics
  • Transplantation Immunology

Substances

  • Receptors, Antigen, T-Cell