SKY analysis revealed recurrent numerical and structural chromosome changes in BDII rat endometrial carcinomas

Abstract

BackgroundGenomic alterations are common features of cancer cells, and some of these changes are proven to be neoplastic-specific. Such alterations may serve as valuable tools for diagnosis and classification of tumors, prediction of clinical outcome, disease monitoring, and choice of therapy as well as for providing clues to the location of crucial cancer-related genes.Endometrial carcinoma (EC) is the most frequently diagnosed malignancy of the female genital tract, ranking fourth among all invasive tumors affecting women. Cytogenetic studies of human ECs have not produced very conclusive data, since many of these studies are based on karyotyping of limited number of cases and no really specific karyotypic changes have yet been identified. As the majority of the genes are conserved among mammals, the use of inbred animal model systems may serve as a tool for identification of underlying genes and pathways involved in tumorigenesis in humans. In the present work we used spectral karyotyping (SKY) to identify cancer-related aberrations in a well-characterized experimental model for spontaneous endometrial carcinoma in the BDII rat tumor model.ResultsAnalysis of 21 experimental ECs revealed specific nonrandom numerical and structural chromosomal changes. The most recurrent numerical alterations were gains in rat chromosome 4 (RNO4) and losses in RNO15. The most commonly structural changes were mainly in form of chromosomal translocations and were detected in RNO3, RNO6, RNO10, RNO11, RNO12, and RNO20. Unbalanced chromosomal translocations involving RNO3p was the most commonly observed structural changes in this material followed by RNO11p and RNO10 translocations.ConclusionThe non-random nature of these events, as documented by their high frequencies of incidence, is suggesting for dynamic selection of these changes during experimental EC tumorigenesis and therefore for their potential contribution into development of this malignancy. Comparative molecular analysis of the identified genetic changes in this tumor model with those reported in the human ECs may provide new insights into underlying genetic changes involved in EC development and tumorigenesis.

The impact of the genetic background on the genome make‐up of tumor cells

“…The SKY technique was used to examine the karyotypes of 21 rat EAC tumor cell lines and one normal rat embryo fibroblast (REF) cell culture (Falck et al, 2011). In one of the tumor cell lines, NUT42, only six metaphases could be analyzed and therefore, this cell line was omitted from the following analysis.…”

“…In a previous report, 21 rat EACs were analyzed by SKY (Falck et al, 2011). Substantial amount of data were produced from this analysis, and the results needed to be carefully scrutinized for an improved discovery of recurrent chromosomal changes in EAC tumors (Falck et al, 2011).…”

“…The distribution of ploidies differed significantly between backgrounds ( P < 0.001). * adopted from (Falck et al, 2011).…”

“…The data on numerical changes are not related to the ploidy level and were collected separately. Apart from that the different steps in the SKY procedure; hybridization, detection, and the analysis of the results are described in detail in Falck et al 2011.…”

“…In a previous study a set of 21 rat EACs cell lines derived from tumors developed in female crossprogenies between BDII and nonsusceptible rat strains were analyzed by SKY (Falck et al, 2011). In the present work the impact of the genetic set up of the two nonsusceptible parental strains on the development of EAC was scrutinized, and in addition we have identified the contribution to tumorigenesis from the susceptible strain.…”