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

doi:10.1038/ng1521

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

Hematology

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Pages (from-to)	265-274
Number of pages	10
Journal	Nature Genetics
Volume	37
Issue number	3
DOIs	https://doi.org/10.1038/ng1521
State	Published - Mar 1 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

Yu, L, Liu, C, Vandeusen, J, Becknell, B, Dai, Z, Wu, YZ, Raval, A, Liu, TH, Ding, W, Mao, C, Liu, S, Smith, LT, Lee, S, Rassenti, L, Marcucci, G, Byrd, J, Caligiuri, MA & 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, vol. 37, no. 3, pp. 265-274. https://doi.org/10.1038/ng1521

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

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.",

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

note = "Funding Information: We thank S. Liyanarachchi for statistical help. This work was supported in part by grants from the US Public Health Service (to C.P. and M.A.C.). C.P. and J.B. are Leukemia and Lymphoma Society of America Scholars.",

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AU - Wu, Yue Zhong

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AU - Marcucci, Guido

AU - Byrd, John

AU - Caligiuri, Michael A.

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N1 - Funding Information: We thank S. Liyanarachchi for statistical help. This work was supported in part by grants from the US Public Health Service (to C.P. and M.A.C.). C.P. and J.B. are Leukemia and Lymphoma Society of America Scholars.

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AB - 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.

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

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