Molecular cytogenetic analysis of chemoresistant non-Hodgkin's lymphoma patients with p53 abnormalities using fluorescence in situ hybridisation and comparative genomic hybridisation.

Abstract

Alterations of the p53 gene at 17p13.1 as well as the gene for a transmembrane p-glycoprotein, ABCB1 (MDR-1) at 7q21.12, have been shown to be mostly associated with the phenomenon of multi-drug resistance (MDR) in human cancers. In order to better understand the mechanisms by which chemoresistance is mediated, non-hodgkin's lymphoma (NHL) patients overexpressing p53 mutant protein and resistant to CHOP chemotherapy, NHL patients without p53 overexpression and a Burkitt's lymphoma Raji cell line with p53 overexpression have been evaluated using fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH). Three chromosomes (1, 7, and 17) known to be associated with MDR and the presence of p53 mutant protein, were analysed by FISH. No obvious chromosomal aberrations such as translocations were found in any of the patients when compared to healthy individuals, which suggests that the three selected chromosomes might not be specifically related to NHL, with or without p53 overexpression. For CGH, gains and losses of chromosomal material have been identified and the changes were not only limited to the three selected chromosomes associated with MDR. A detailed analysis of the recurrent aberrations shows that most of the NHL patients have alterations on the chromosome arms 1p, 6q, 7q, 20q, 22q, and Xp, whereas patients with p53 overexpression predominantly show aberrations on 4p and 17q. Further characterisation of the genetic regions identified might more closely contribute to our understanding of acquired MDR in NHL. Alterations in the three evaluated chromosomes may be prevalent in other tumours. In the present study, using FISH and CGH, there was insufficient difference between NHL patients with and without p53 overexpression.