A Preliminary Report on Microarray Based Identification of Genes Involved in Drug Resistance in Retinoblastoma

Abstract

Purpose: : Whole genome microarray in retinoblastoma post chemotherapy has not been studied. A study like this would generate data on the genes and the pathways involved in drug resistance and tumour proliferation. In this preliminary study, we report on the whole genome microarray on a retinoblastoma tumour, which was enucleated post 10 cycles of triple chemotherapy due to non responsiveness.

Methods: : We compared the gene expression profile of the chemo-treated retinoblastoma tumor with that of a tumor enucleated without prior chemotherapy. Differential gene expression profiling was performed on Affymetrix microarray platform. Agilent Feature Extraction software (G25677AA, Agilent Technologies, 2004) was used to analyze the microarray data.

Results: : The microarray analysis identified 417 genes to be deregulated, of which 185 were up regulated and 232 were down-regulated. The deregulated proteins belonged to various functional categories such as cell proliferation, transporter activity, signal transduction activity, cell cycle and protein binding activity. Interestingly, genes that are involved in chemotherapy resistance such as ABCA1 (ATP binding cassette proteins), PTGS2 (prostaglandin synthase 2), BCL2L1 (BCL2 like 1), IL13RA1 (Interleukin 13 receptor alpha 1), PRAME (preferentially expressed antigen in melanoma), IL6 (Interleukin 6), MHC class 1 (Major histo-compatability class 1) are significantly up regulated in the chemo resistant-retinoblastoma when compared to no chemo treated-retinoblastoma. On the other hand, MCJ protein (Methylation controlled J) was significantly down regulated. MCJ inhibits c-Jun-mediated expression of ABCB1 (P-glycoprotein) and maintain drug response.

Conclusions: : This is the first preliminary report on the gene expression variations in the retinoblastoma tumour treated with triple-chemotherapy regimen. Although preliminary, this data give us a clue on how the genes are regulated in chemotherapy treated case and further a large cohort with validation and in vitro studies are warranted to understand the biologically meaningful role of these genes in drug resistance

Keywords: oncology • retinoblastoma • pathobiology