Scott, Clare LGil, JesúsHernando, EvaTeruya-Feldstein, JulieNarita, MasakoMartinez Garcia, Maria DoloresVisakorpi, TapioMu, DavidCordon-Cardo, CarlosPeters, GordonBeach, DavidLowe, Scott W2024-02-012024-02-012007-03-27Proc Natl Acad Sci U S A . 2007;104(13):5389-94.0027-8424http://hdl.handle.net/20.500.12105/17407Chromobox 7 (CBX7) is a chromobox family protein and a component of the Polycomb repressive complex 1 (PRC1) that extends the lifespan of cultured epithelial cells and can act independently of BMI-1 to repress the INK4a/ARF tumor suppressor locus. To determine whether CBX7 might be oncogenic, we examined its expression pattern in a range of normal human tissues and tumor samples. CBX7 was expressed at high levels in germinal center lymphocytes and germinal center-derived follicular lymphomas, where elevated expression correlated with high c-Myc expression and a more advanced tumor grade. By targeting Cbx7 expression to the lymphoid compartment in mice, we showed that Cbx7 can initiate T cell lymphomagenesis and cooperate with c-Myc to produce highly aggressive B cell lymphomas. Furthermore, Cbx7 repressed transcription from the Ink4a/Arf locus and acted epistatically to the Arf-p53 pathway during tumorigenesis. These data identify CBX7 as a chromobox protein causally linked to cancer development and may help explain the low frequency of INK4a/ARF mutations observed in human follicular lymphoma.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/MutationAnimalsCyclin-Dependent Kinase Inhibitor p16Epithelial CellsHumansLoss of HeterozygosityLymphomaMiceNeoplasmsNuclear ProteinsPolycomb Repressive Complex 1Polycomb-Group ProteinsProto-Oncogene Proteins c-mycRepressor ProteinsT-LymphocytesTumor Suppressor Protein p53Attribution-NonCommercial-NoDerivatives 4.0 Internacional1737472210413538910.1073/pnas.0608721104Proceedings of the National Academy of Sciences of the United States of Americaopen access