Tetraploidy and chromosomal instability are early events during cervical carcinogenesis

Abstract

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.

Pharmacogenetic profiling of Aurora kinase B is associated with overall survival in metastatic colorectal cancer

“…Numerous studies have shown that the loss of mitotic regulation contributes to carcinogenesis. [26][27][28] Any inaccuracies during the process of chromosomal segregation results in either a loss or gain of chromosomes, potentially leading to upregulation of oncogenes or down regulation of tumor supressors. 29 Recent in vivo data from Ramadan et al 20 suggests AURKB to be responsible for the prevention of chromatin decondensation during late mitosis.…”

Centrosome amplification induced by survivin suppression enhances both chromosome instability and radiosensitivity in glioma cells

“…A number of studies have demonstrated that the suppression of survivin results in cells with multipolar mitotic spindles that are either multinucleated or aneuploid (Li et al, 1999;Beltrami et al, 2004;Kappler et al, 2004). Some studies have also indicated that aneuploidy promotes chromosome instability (CIN) in glioma and cervical carcinoma cells (Nitta et al, 2002;Olaharski et al, 2006).…”

Assessment of mutagenic and antimutagenic effects of Punica granatum in mice

“…The in vivo mouse bone marrow micronucleus (MN) assay is currently recommended by the International Conference on Harmonization (ICH, 1997), the Food and Drug Administration, and other regulatory agencies (Cimino, 2006) to investigate the genotoxic/ chemopreventive potential of new agents. In addition, a direct connection between increase in MN frequency and development of carcinogenesis has been documented in the literature (Olaharski et al, 2006).…”