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We aimed to identify the critical molecular pathways altered upon tumor stroma interactions in retinoblastoma (RB). In vitro 2 D cocultures of RB tumor cells (Weri-Rb-1 and NCC-RbC-51) with primary bone marrow stromal cells (BMSC) was established. Global gene expression patterns in coculture samples were assessed using Affymetrix Prime view human gene chip microarray and followed with bioinformatics analyses. Key upregulated genes from Weri-Rb-1 + BMSC and NCC-RbC-51 + BMSC coculture were validated using qRT-PCR to ascertain their role in RB progression. Whole genome microarray experiments identified significant (P ≤ 0.05, 1.1 log 2 FC) transcriptome level changes induced upon coculture of RB cells with BMSC. A total of 1155 genes were downregulated and 1083 upregulated in Weri-Rb-1 + BMSC coculture. Similarly, 1865 genes showed downregulation and 1644 genes were …