title: Amplified RPS6KB1 and CDC2 genes are potential biomarkers for aggressive HIV+/EBV+ diffuse large B-cell lymphomas.
abstract: RPS6KB1 encodes p70S6K/p85S6K, which plays a role in the PI3K/Akt/mTOR signal transduction pathway. CDC2 gene encodes cdc2, which is critical for G2/M cell cycle progression. We had previously shown that amplified RPS6KB1 and CDC2 are commonly detected in the EBV+ diffuse large B-cell lymphoma (DLBCL) in HIV patients. In current study, we further evaluated the amplified RPS6KB1 and CDC2 genes in 12 HIV-related aggressive B-cell lymphomas and 10 non-HIV-related DLBCL using real time quantitative PCR. The cases were divided into 4 groups: 1) HIV-/EBV-; 2) HIV-/EBV+; 3) HIV+/EBV-; and 4) HIV+/EBV+. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) was used to assess the ability of each gene to distinguish non-HIV+/EBV+ cases from HIV+/EBV+ cases. The AUC was estimated to be 0.76 for RPS6KB1 and 0.74 for CDC2 by using the Mann-Whitney statistic. Amplified RPS6KB1 and CDC2 genes were more frequently detected in common variants of DLBCL associated with HIV infection. Taken together, amplified RPS6KB1 and CDC2 are potential biomarkers for the aggressive DLBCL, particularly in HIV+/EBV+ patients. This study also suggests that the HIV+/EBV+ aggressive DLBCL could be potentially treated by targeting RPS6KB1 and CDC2 genes.
authors: Department of Pathology, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA. Frank.Zhao2@va.gov
authors: Xianfeng F
authors: XF
authors: Zhao
authors: Merry Y
authors: MY
authors: Zhao
authors: Ling
authors: L
authors: Chai
authors: Debra
authors: D
authors: Kukuruga
authors: Ming
authors: M
authors: Tan
authors: Sanford A
authors: SA
authors: Stass
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D016203:CDC2 Protein Kinase; D002455:Cell Division / Q000235:genetics; D019926:Cyclin B / Q000235:genetics*; D018844:Cyclin-Dependent Kinases; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D016195:G2 Phase / Q000235:genetics; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000235:genetics* / Q000473:pathology / Q000821:virology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology / Q000821:virology; D012372:ROC Curve; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D019926:Cyclin B; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases
keywords: CDC2; EBV; HIV; RPS6KB1; biomarker; lymphoma