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


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.


CONCLUSIONS
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.
Poirel
Hélène A
HA
Centre de génétique, Hematological section of the Center of Human Genetics, Cliniques Universitaires St-Luc-UCL, Bruxelles, Belgium.
Bernheim
Alain
A
Schneider
Anouck
A
Meddeb
Mounira
M
Choquet
Sylvain
S
Leblond
Véronique
V
Charlotte
Frédéric
F
Davi
Frédéric
F
Canioni
Danielle
D
Macintyre
Elizabeth
E
Mamzer-Bruneel
Marie-France
MF
Hirsch
Isabelle
I
Hermine
Olivier
O
Martin
Antoine
A
Cornillet-Lefebvre
Pascale
P
Patey
Martine
M
Toupance
Olivier
O
Kémény
Jean-Louis
JL
Deteix
Patrice
P
Raphaël
Martine
M
D000328:Adult; D002648:Child; D002675:Child, Preschool; D043171:Chromosomal Instability / Q000235:genetics*; D002874:Chromosome Mapping; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D011183:Postoperative Complications / Q000503:physiopathology / Q000821:virology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D014181:Transplantation Immunology
D011948:Receptors, Antigen, T-Cell