JC human polyomavirus is associated to chromosomal instability in peripheral blood lymphocytes of Hodgkin's lymphoma patients and poor clinical outcome
Résumé
Background: B cells are potential sites for latency and reactivation of the human neurotropic JC polyomavirus (JCV). We investigated JCV and Epstein-Barr virus (EBV) status in peripheral blood lymphocytes (PBL) from 74 Hodgkin's lymphoma (HL) and 91 B-cell non-Hodgkin's lymphoma (B-NHL) patients. Patients and methods: JCV and EBV DNA were assessed by PCR, and FISH technique was used to localize viral infection and to estimate chromosomal instability (rogue cells, 'chromosomal aberrations') throughout evolution. The influence of viral infection and chromosomal instability on freedom from progression (FFP) was investigated in HL patients. Results: PCR product sequencing of PBL identified JCV in 42 (57%) circulating lymphocytes of HL patients. FISH analysis revealed that the presence of cells with a high JCV genome copy number-associated to the presence of rogue cells and 'higher frequency of chromosomal aberrations'-increased from 15% before treatment to 52% (P < 10-5) after. The co-activation of JCV and EBV was independent of known prognostic parameters and associated with a shorter FFP (JCV and EBV co-activation P < 0.001, rogue cells P < 0.002). Conclusion: In HL, JCV activation and chromosomal instability have been identified in PBL and associated with a poorer prognosis, especially in EBV+. © The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.
Mots clés
article
cancer growth
chromosomal instability
controlled study
Epstein Barr virus
female
fluorescence in situ hybridization
gene dosage
Hodgkin disease
human
human cell
JC virus
major clinical study
male
nonhuman
nucleotide sequence
outcome assessment
peripheral lymphocyte
polymerase chain reaction
priority journal
prognosis
virus activation
virus infection
Adolescent
Adult
Aged
Base Sequence
Chromosomal Instability
Epstein-Barr Virus Infections
Female
Herpesvirus 4
Human
Hodgkin Disease
Humans
JC Virus
Lymphocytes
Male
Middle Aged
Molecular Sequence Data
Polyomavirus Infections
Prevalence
Prognosis
Retrospective Studies
Tumor Virus Infections
Young Adult
alkylating agent
anthracycline
podophyllotoxin
adult