Carcinogenesis Advance Access published online on August 25, 2005
Carcinogenesis, doi:10.1093/carcin/bgi218
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Environmental Toxicology Graduate Program, Department of Cell Biology & Neuroscience, 5429 Boyce Hall, University of California, Riverside, CA-92521, USA; Current address: School of Public Health, Molecular Epidemiology and Toxicology Laboratory, 140 Warren Hall, University of California, Berkeley, CA
* To whom correspondence should be addressed. Chromosomal instability as manifested by increases in aneuploidy and structural chromosome aberrations is believed to play a critical role in the intermediate to late stages in the development of cervical malignancies. The current study was designed to determine the role of tetraploidy in the formation of aneuploidy and ascertain the occurrence of these alterations during the earlier stages of cervical carcinogenesis. Cervical cell samples with diagnoses ranging from Normal to high-grade lesions (HSIL) were obtained from 143 women and were evaluated for chromosomal alterations using dual-probe fluorescence in situ hybridization. Cervical cells from a subset of the group were also evaluated for chromosomal instability in the form of micronuclei. The frequencies of cells exhibiting either tetrasomy or aneusomy for chromosomes 3 & 17 increased significantly with disease progression and displayed distinctive patterns where aneusomy was rarely present in the absence of tetrasomy. The frequencies of micronuclei that formed through either chromosomal loss or breakage increased significantly in both the low- and high-grade diagnostic categories and were highly correlated with both the number of tetrasomic and aneusomic cervical cells. In addition, a unique chromosomal alteration involving a significant non-random loss of chromosome 17 specific to near-tetraploid aneusomic cells (trisomy 17 and tetrasomy 3) was observed. We conclude that tetraploidy and chromosomal instability are related events occurring during the early stages of cervical carcinogenesis that predispose cervical cells to the formation of aneuploidy frequently involving the loss of chromosome 17.
Received April 23, 2005
Revised July 28, 2005
Accepted August 19, 2005
CARCINOGENESIS
Tetraploidy and chromosomal instability are early events during cervical carcinogenesis
2 Mexican National Cancer Institute, Mexico City, Mexico
3 Department of Genomic Medicine and Environmental Toxicology, National Autonomous University of Mexico (UNAM), Mexico City, Mexico
4 Mexican National Cancer Institute, Mexico City, Mexico; Department of Genomic Medicine and Environmental Toxicology, National Autonomous University of Mexico (UNAM), Mexico City, Mexico
5 Environmental Toxicology Graduate Program, Department of Cell Biology & Neuroscience, 5429 Boyce Hall, University of California, Riverside, CA-92521, USA
David A. Eastmond, E-mail: david.eastmond{at}ucr.edu
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. G. Nguyen, M. Makitalo, D. Yang, D. Chinnappan, C. St. Hilaire, and K. Ravid Deregulated Aurora-B induced tetraploidy promotes tumorigenesis FASEB J, August 1, 2009; 23(8): 2741 - 2748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Heilman, J. J. Nordberg, Y. Liu, G. Sluder, and J. J. Chen Abrogation of the Postmitotic Checkpoint Contributes to Polyploidization in Human Papillomavirus E7-Expressing Cells J. Virol., March 15, 2009; 83(6): 2756 - 2764. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Storchova and C. Kuffer The consequences of tetraploidy and aneuploidy J. Cell Sci., December 1, 2008; 121(23): 3859 - 3866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Shen, D. M. Moran, and C. G. Maki Transient Nutlin-3a Treatment Promotes Endoreduplication and the Generation of Therapy-Resistant Tetraploid Cells Cancer Res., October 15, 2008; 68(20): 8260 - 8268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Hufton, D. Groth, M. Vingron, H. Lehrach, A. J. Poustka, and G. Panopoulou Early vertebrate whole genome duplications were predated by a period of intense genome rearrangement Genome Res., October 1, 2008; 18(10): 1582 - 1591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhai, R. Kuick, B. Nan, I. Ota, S. J. Weiss, C. L. Trimble, E. R. Fearon, and K. R. Cho Gene Expression Analysis of Preinvasive and Invasive Cervical Squamous Cell Carcinomas Identifies HOXC10 as a Key Mediator of Invasion Cancer Res., November 1, 2007; 67(21): 10163 - 10172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu, S. A. Heilman, D. Illanes, G. Sluder, and J. J. Chen p53-Independent Abrogation of a Postmitotic Checkpoint Contributes to Human Papillomavirus E6-Induced Polyploidy Cancer Res., March 15, 2007; 67(6): 2603 - 2610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bonassi, A. Znaor, M. Ceppi, C. Lando, W. P. Chang, N. Holland, M. Kirsch-Volders, E. Zeiger, S. Ban, R. Barale, et al. An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans Carcinogenesis, March 1, 2007; 28(3): 625 - 631. [Abstract] [Full Text] [PDF]
|
|