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The impact of the genetic background on the genome make-up of tumor cells
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Systems Biology Research Centre - Tumor Biology, School of Life Sciences, University of Skövde, Skövde, Sweden.
Systems Biology Research Centre - Tumor Biology, School of Life Sciences, University of Skövde, Skövde, Sweden; Department of Medical and Clinical Genetics, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Systems Biology Research Centre - Tumor Biology, School of Life Sciences, University of Skövde, Skövde, Sweden.
2012 (English)In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 51, no 5, p. 438-446Article in journal (Refereed) Published
Abstract [en]

Endometrial adenocarcinoma (EAC) is the most common form of malignancy in the female genital tract, ranking as the fourth leading form of invasive tumors that affect women. The BDII inbred rat strain has been used as a powerful tumor model in studies of the genetic background of EAC. Females from the BDII strain are prone to develop tumors with an incidence of more than 90%. Development of EAC in BDII female rats has similarities in pathogenesis, histopathological, and molecular properties to that of human, and thus represents a unique model for analysis of EAC tumorigenesis and for comparative studies in human EACs. In a previous study, a set of rat EAC cell lines derived from tumors developed in female crossprogenies between BDII and nonsusceptible rat strains were analyzed by spectral karyotyping (SKY). Here we present an analysis with specific focus on the impact of different genetic backgrounds on the rate and occurrence of genetic aberrations in experimental tumors using data presented in the previous report. We could reveal that the ploidy state, and the abundance and type of structural as well as numerical change differed between the two genetic setups. We have also identified chromosomes harboring aberrations independent of genetic input from the nonsusceptible strains, which provide valuable information for the identification of the genes involved in the development of EAC in the BDII model as well as in human endometrial tumors. (C) 2012 Wiley Periodicals, Inc.

Place, publisher, year, edition, pages
Malden, USA: Wiley-Blackwell, 2012. Vol. 51, no 5, p. 438-446
National Category
Medical and Health Sciences Cancer and Oncology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-22309DOI: 10.1002/gcc.21929ISI: 000301118100003PubMedID: 22250046Scopus ID: 2-s2.0-84857997916OAI: oai:DiVA.org:oru-22309DiVA, id: diva2:513416
Note

Funding Agencies:

Royal Physiographic Society in Lund (Nilsson-Ehle Foundation)

Stiftelsen Wilhelm och Martina Lundgrens Vetenskapsfond 

Royal Society of Arts and Sciences in Gothenburg 

Erik Philip-Sorensen Foundation 

Available from: 2012-04-02 Created: 2012-04-02 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Genomic and genetic alterations in endometrial adenocarcinoma
Open this publication in new window or tab >>Genomic and genetic alterations in endometrial adenocarcinoma
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The most frequently diagnosed cancer of the female genital tract is cancer of the endometrium (endometrial cancer), ranking fourth among the invasive tumors that affect women in Europe and North America. As most other cancer types, endometrial cancer is a complex genetic disease influenced by both genetic and environmental factors.

The human population is genetically heterogeneous and studies of complex diseases in human are proven to be difficult. By using a model system such as the BDII rat, some of the obstacles related to the study of complex diseases can be avoided. The BDII rat strain is prone to spontaneously develop endometrial adenocarcinoma (EAC) and more than 90% of the virgin females develop EAC during their lifetime. Development of EAC tumors in BDII rats is comparable in pathogenesis and histopathological properties to that of human.

The aims of this thesis were i/ to characterize EAC in the BDII rat experimental model system by analyzing structural and numerical chromosome aberrations, ii/ to evaluate the importance of the genetic set-up in EAC development, and iii/ to determine the impact of genomic and genetic alterations on the functionality of candidate genes in rat EAC and in human endometrial tumors of different FIGO grades.

Non-random numerical and structural aberrations that could contribute to tumor formation were identified, and evidence that the genetic background had a significant influence on the genome make-up of tumor cells was provided. Certain genes (Gpx3/GPX3, Met/MET, Phf5a/PHF5A, and Gja1/GJA1) were selected for further analysis and aberrant expression of some of them were found in both rat and human EACs. By separating EAC cell lines according to the genetic cross background, for two of the genes (Phf5 and Met), we showed that the expression pattern differed significantly between different cross backgrounds, which clearly pinpoint the importance of using animal models as a complement to clinical studies in identification of cancer-related genes.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2013
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 81
Keywords
Endometrial cancer, Genetic background, BDII rat model, SKY, Chromosomal abreations, Gene expression
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-26881 (URN)978-91-7668-913-4 (ISBN)
Public defence
2013-03-01, Insikten, Högskolan i Skövde, Skövde, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2013-01-16 Created: 2013-01-16 Last updated: 2017-10-17Bibliographically approved

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