Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia

Li Yu, Chunhui Liu, Jeff Vandeusen, Brian Becknell, Zunyan Dai, Yue Zhong Wu, Aparna Raval, Te Hui Liu, Wei Ding, Charlene Mao, Shujun Liu, Laura T. Smith, Stephen Lee, Laura Rassenti, Guido Marcucci, John Byrd, Michael A. Caligiuri, Christoph Plass

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158 Scopus citations

Abstract

DNA methylation is associated with malignant transformation, but limitations imposed by genetic variability, tumor heterogeneity, availability of paired normal tissues and methodologies for global assessment of DNA methylation have limited progress in understanding the extent of epigenetic events in the initiation and progression of human cancer and in identifying genes that undergo methylation during cancer. We developed a mouse model of T/natural killer acute lymphoblastic leukemia that is always preceded by polyclonal lymphocyte expansion to determine how aberrant promoter DNA methylation and consequent gene silencing might be contributing to leukemic transformation. We used restriction landmark genomic scanning with this mouse model of preleukemia reproducibly progressing to leukemia to show that specific genomic methylation is associated with only the leukemic phase and is not random. We also identified Idb4 as a putative tumor-suppressor gene that is methylated in most mouse and human leukemias but in only a minority of other human cancers.

Original languageEnglish (US)
Pages (from-to)265-274
Number of pages10
JournalNature Genetics
Volume37
Issue number3
DOIs
StatePublished - Dec 9 2005

ASJC Scopus subject areas

  • Genetics

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    Yu, L., Liu, C., Vandeusen, J., Becknell, B., Dai, Z., Wu, Y. Z., Raval, A., Liu, T. H., Ding, W., Mao, C., Liu, S., Smith, L. T., Lee, S., Rassenti, L., Marcucci, G., Byrd, J., Caligiuri, M. A., & Plass, C. (2005). Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia. Nature Genetics, 37(3), 265-274. https://doi.org/10.1038/ng1521