Journal article
Cell of origin strongly influences genetic selection in a mouse model of T-ALL
Blood, Vol.118(17), pp.4646-4656
10/27/2011
DOI: 10.1182/blood-2011-03-343947
PMCID: PMC3208280
PMID: 21828136
Abstract
Identifying the normal cell from which a tumor originates is crucial to understanding the etiology of that cancer. However, retrospective identification of the cell of origin in cancer is challenging because of the accumulation of genetic and epigenetic changes in tumor cells. The biologic state of the cell of origin likely influences the genetic events that drive transformation. We directly tested this hypothesis by performing a Sleeping Beauty transposon mutagenesis screen in which common insertion sites were identified in tumors that were produced by mutagenesis of cells at varying time points throughout the T lineage. Mutation and gene expression data derived from these tumors were then compared with data obtained from a panel of 84 human T-cell acute lymphoblastic leukemia samples, including copy number alterations and gene expression profiles. This revealed that altering the cell of origin produces tumors that model distinct subtypes of human T-cell acute lymphoblastic leukemia, suggesting that even subtle changes in the cell of origin dramatically affect genetic selection in tumors. These findings have broad implications for the genetic analysis of human cancers as well as the production of mouse models of cancer.
Details
- Title: Subtitle
- Cell of origin strongly influences genetic selection in a mouse model of T-ALL
- Creators
- Katherine E Berquam-Vrieze - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA, USAKishore Nannapaneni - University of IowaBenjamin T Brett - University of IowaLinda Holmfeldt - St. Jude Children's Research HospitalJing Ma - St. Jude Children's Research HospitalOksana Zagorodna - University of IowaNancy A Jenkins - University of IowaNeal G Copeland - University of IowaDavid K Meyerholz - University of IowaC Michael Knudson - University of IowaCharles G Mullighan - St. Jude Children's Research HospitalTodd E Scheetz - University of IowaAdam J Dupuy - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.118(17), pp.4646-4656
- Publisher
- United States
- DOI
- 10.1182/blood-2011-03-343947
- PMID
- 21828136
- PMCID
- PMC3208280
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Grant note
- 5R01CA130867 / NCI NIH HHS T32 GM008629 / NIGMS NIH HHS R01 CA130867 / NCI NIH HHS
- Language
- English
- Date published
- 10/27/2011
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Anatomy and Cell Biology; Pathology; Radiation Oncology; Ophthalmology and Visual Sciences
- Record Identifier
- 9983979974102771
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