Molecular analysis of LMP-1 oncogene in pediatric Hodgkin`s disease

PRECIADO, M. V.; DE MATTEO, E; BONGI, R.; REY, G.; PAOLA ANDREA CHABAY; GRINSTEIN, S.

Philadelphia

Congreso; American Association for Cancer Research: 90th Annual Meeting; 1999

LMP-1 is a proto-oncogene of the Epstein Barr virus (EBV) that is expressed within the diagnostic Hodgkin and Reed-Sternberg cells (H-RS) of HD. Under in vitro conditions, deletions of the C-terminal of LMP-1 were associated with prolongation of its half-life. Ten pediatric (2-15 years) HD patients (mixed cellularity n=9 and lymphocyte predominant n=1 and stage I n=1, II n=8, III n=1) which were LMP-1+ by immunohistochemistry were studied. In each case, viral DNA of the C-terminal domain of LMP-1 was amplified by PCR and sequenced. LMP-1 deletions and point mutations at the C-terminal domain were correlated with EBV-strain type, histological characteristics and survival of patients. The 30-bp deletion, spanned from codon 346 through codon 355, was identified in 6/10 cases (3/6 EBV-1 and 3/4 EBV-2). Some point mutations were also found in all cases. LMP-1 deletion was histologically associated with a significant (p=0.03) high number of LMP-1 and EBERs+ H-RS cells , however there was no correlation with patient’s survival. These findings suggest that the 30bp deletion may correlate with a histologically aggressive behaviour of pediatric HD and both EBV types are involved in the same magnitude, but an eventual clinical significance of the 30bp deletion remains to be determined in a higher number of patients.