Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures

To glean biological differences and similarities of peripheral T-cell lymphoma–not otherwise specified [PTCL-NOS] to diffuse large B-cell lymphoma (DLBCL), a transcriptosome analysis was done on five PTCL-NOS and four DLBCL patients and validated by quantitative real-time reverse transcription-PCR on 10 selected genes. Normal peripheral blood T cells, peripheral blood B cells, and lymph node were used as controls. The resultant gene expression profile delineated distinct “tumor profile signatures” for PTCL-NOS and DLBCL. Several highly overexpressed genes in both PTCL-NOS and DLBCL involve the immune network, stroma, angiogenesis, and cell survival cascades that make important contributions to lymphomagenesis. Inflammatory chemokines and their receptors likely play a central role in these complex interrelated pathways: CCL2 and CXCR4 in PTCL-NOS and CCL5 and CCR1 in DLBCL. Highly overexpressed oncogenes unique to PTCL-NOS are SPI1, STK6, α-PDGFR , and SH2D1A , whereas in DLBCL they are PIM1, PIM2, LYN, BCL2A1 , and RAB13 . Oncogenes common to both lymphomas are MAFB, MET, NF-κB2, LCK , and LYN . Several tumor suppressors are also down-regulated ( TPTE, MGC154, PTCH, ST5 , and SUI1 ). This study illustrates the relevance of tumor-stroma immune trafficking and identified potential novel prognostic markers and targets for therapeutic intervention. [Mol Cancer Ther 2005;4(12):1867–79]