Journal Article

Tetraploidy and chromosomal instability are early events during cervical carcinogenesis

Andrew J. Olaharski, Rita Sotelo, Gilberto Solorza-Luna, Maria E. Gonsebatt, Patricia Guzman, Alejandro Mohar and David A. Eastmond

in Carcinogenesis

Volume 27, issue 2, pages 337-343
Published in print February 2006 | ISSN: 0143-3334
Published online August 2005 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/bgi218
Tetraploidy and chromosomal instability are early events during cervical carcinogenesis

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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 and 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-grade 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.

Keywords: ASCUS, atypical squamous cells of undetermined significance; DAPI, 4′,6-Diamidino-2-phenylindole; FISH: fluorescence in situ hybridization; HSIL, high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion; SSC, saline–sodium citrate

Journal Article.  5956 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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