PCC and COBRA-FISH a new tool to characterize primary cervical carcinomas: to assess hall-marks and stage specificity.
A newly developed assay based on chemically induced premature chromosome condensation (PCC) and multi-color combined binary ratio labeling (COBRA) fluorescence in situ hybridization (FISH) techniques have been implemented in order to investigate for the first time for recurrent cytogenetic aberrations in primary cervical carcinoma (derived directly from biopsies) at different stages of progression. The cytogenetic profiles of 17 biopsies derived from 14 and 3 cervical cancer patients with squamous-cell carcinomas (Sq) and with adenocarcinomas (Ad), respectively, were assessed. Frequencies of both structural as well as numerical aberrations were found to be higher in Sq than in Ad. The analysis revealed that even in early tumors stages (IB1) have a higher frequency of chromosome-losses and -gains as well as chromosomal alterations as compared to normal cells. A positive trend was found between stage advancement of cervical tumors and the frequency of numerical and structural aberrations. No specific and common chromosomal abnormality (e.g. distinct clones of translocation) was found among cervical carcinoma at the different stages (IB1, IIA and IIB). However, a distinct difference was found between stage IIIB and lower tumor stages, as all analyzed IIIB samples revealed a near tetraploid karyotype. Furthermore, all studied metaphases were aberrant and had a high frequency of translocations. PCC-COBRA-FISH characterization of a common type of an established culture from cervical carcinoma CSCC-1 revealed a triploidy/tetraploidy karyotype with several structural aberrations. In general, no similarity was found between this model and early stages of primary tumors. The newly established assay has a novel potential and can reveal the original status of primary tumors at different stages.
Darroudi
Firouz
F
Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, 2300RC Leiden, The Netherlands. F.Darroudi@LUMC.NL
Bergs
Judith W J
JW
Bezrookove
Vladimir
V
Buist
Marrije R
MR
Stalpers
Lukas J
LJ
Franken
Nicolaas A P
NA
D000230:Adenocarcinoma / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000378:metabolism*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007621:Karyotyping; D009367:Neoplasm Staging; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology