Annals of Oncology Advance Access published online on October 13, 2009
Annals of Oncology, doi:10.1093/annonc/mdp375
JC human polyomavirus is associated to chromosomal instability in peripheral blood lymphocytes of Hodgkin’s lymphoma patients and poor clinical outcome
1 Cell & Environment, Paris
2 Laboratory of Radiation Sensitivity and Radio-carcinogenesis UPRES EA 27-10, Institut Gustave Roussy, Villejuif
3 Laboratory of Virology IFR53/EA-3798, Reims
4 Inserm U362, Institut Gustave Roussy, Villejuif
5 Laboratory of Radiopathology, Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses
6 Department of Medicine
7 Cellular Genomics of Cancers Laboratory CNRS-UMR 1599
8 Department of Biostatistics
9 Department of Pathology, Institut Gustave Roussy, Villejuif, France
* Correspondence to: Dr R. M'kacher, Cell & Environment, 88bis rue des Pyrénées, 75020 Paris, France. Tel: +33-1-42-11-42-88; Fax: +33-1-42-11-52-36; E-mail: mkacher{at}igr.fr
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+.
chromosomal instability, clinical outcome, Hodgkin’s lymphoma, JC virus, non-Hodgkin’s lymphoma, rogue cell
Both authors contributed equally to this work. Received for publication April 13, 2009. Revision received June 9, 2009. Accepted for publication June 23, 2009.