This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Upender, M. B. Articles by Ried, T. Search for Related Content PubMed PubMed Citation Articles by Upender, M. B. Articles by Ried, T.

Chromosome Transfer Induced Aneuploidy Results in Complex Dysregulation of the Cellular Transcriptome in Immortalized and Cancer Cells

¹ Genetics Branch and ² Laboratory for Biosystems and Cancer, Center for Cancer Research and ³ Biometric Research Branch, National Cancer Institute/NIH, Bethesda, Maryland; and ⁴ Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institute, Stockholm, Sweden

Chromosomal aneuploidies are observed in essentially all sporadic carcinomas. These aneuploidies result in tumor-specific patterns of genomic imbalances that are acquired early during tumorigenesis, continuously selected for and faithfully maintained in cancer cells. Although the paradigm of translocation induced oncogene activation in hematologic malignancies is firmly established, it is not known how genomic imbalances affect chromosome-specific gene expression patterns in particular and how chromosomal aneuploidy dysregulates the genetic equilibrium of cells in general. To model specific chromosomal aneuploidies in cancer cells and dissect the immediate consequences of genomic imbalances on the transcriptome, we generated artificial trisomies in a karyotypically stable diploid yet mismatch repair-deficient, colorectal cancer cell line and in telomerase immortalized, cytogenetically normal human breast epithelial cells using microcell-mediated chromosome transfer. The global consequences on gene expression levels were analyzed using cDNA arrays. Our results show that regardless of chromosome or cell type, chromosomal trisomies result in a significant increase in the average transcriptional activity of the trisomic chromosome. This increase affects the expression of numerous genes on other chromosomes as well. We therefore postulate that the genomic imbalances observed in cancer cells exert their effect through a complex pattern of transcriptional dysregulation.

This article has been cited by other articles:

				M. F. Reynolds, E. C. Peterson-Roth, I. A. Bespalov, T. Johnston, V. M. Gurel, H. L. Menard, and A. Zhitkovich Rapid DNA Double-Strand Breaks Resulting from Processing of Cr-DNA Cross-Links by Both MutS Dimers Cancer Res., February 1, 2009; 69(3): 1071 - 1079. [Abstract] [Full Text] [PDF]

				J. Camps, M. Grade, Q. T. Nguyen, P. Hormann, S. Becker, A. B. Hummon, V. Rodriguez, S. Chandrasekharappa, Y. Chen, M. J. Difilippantonio, et al. Chromosomal Breakpoints in Primary Colon Cancer Cluster at Sites of Structural Variants in the Genome Cancer Res., March 1, 2008; 68(5): 1284 - 1295. [Abstract] [Full Text] [PDF]

				K. A. Finch, G. Fonseka, D. Ioannou, N. Hickson, Z. Barclay, K. Chatzimeletiou, A. Mantzouratou, A. Handyside, J. Delhanty, and D. K. Griffin Nuclear organisation in totipotent human nuclei and its relationship to chromosomal abnormality J. Cell Sci., March 1, 2008; 121(5): 655 - 663. [Abstract] [Full Text] [PDF]

				C. Gao, K. Furge, J. Koeman, K. Dykema, Y. Su, M. L. Cutler, A. Werts, P. Haak, and G. F. Vande Woude Chromosome instability, chromosome transcriptome, and clonal evolution of tumor cell populations PNAS, May 22, 2007; 104(21): 8995 - 9000. [Abstract] [Full Text] [PDF]

				M. Grade, P. Hormann, S. Becker, A. B. Hummon, D. Wangsa, S. Varma, R. Simon, T. Liersch, H. Becker, M. J. Difilippantonio, et al. Gene Expression Profiling Reveals a Massive, Aneuploidy-Dependent Transcriptional Deregulation and Distinct Differences between Lymph Node-Negative and Lymph Node-Positive Colon Carcinomas Cancer Res., January 1, 2007; 67(1): 41 - 56. [Abstract] [Full Text] [PDF]

				M. Grade, B. M. Ghadimi, S. Varma, R. Simon, D. Wangsa, L. Barenboim-Stapleton, T. Liersch, H. Becker, T. Ried, and M. J. Difilippantonio Aneuploidy-Dependent Massive Deregulation of the Cellular Transcriptome and Apparent Divergence of the Wnt/{beta}-catenin Signaling Pathway in Human Rectal Carcinomas Cancer Res., January 1, 2006; 66(1): 267 - 282. [Abstract] [Full Text] [PDF]