Yazarlar : Berquam-Vrieze KE, Nannanpaneni K, Brett BT, Holmfeldt L, Ma J, Zagorodna O, Jenkins NA, Copeland NG, Meyerholz DK, Knudson CM, Mullighan CG, Scheetz TE, Dupuy AJ.

Yayın : Blood.

Yayın Yılı : 2011

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/21828136

Konu : Lösemi

Literatür İçeriği :  

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 due to the accumulation of genetic and epigenetic changes in tumor cells. The biological 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 was then compared to 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.

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