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SKY analysis revealed recurrent numerical and structural chromosome changes in BDII rat endometrial carcinomas
Systems Biology Research Centre, 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, School of Life Sciences, University of Skövde, Skövde, Sweden.
Systems Biology Research Centre, School of Life Sciences, University of Skövde, Skövde, Sweden; Department of Medical and Clinical Genetics, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
2011 (English)In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 11, p. 20-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Genomic 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.

RESULTS: Analysis 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.

CONCLUSION: The 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.

Place, publisher, year, edition, pages
BioMed Central, 2011. Vol. 11, p. 20-
Keywords [en]
SKY; BDII rat; endometrial carcinoma
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-27559DOI: 10.1186/1475-2867-11-20ISI: 000293340700001PubMedID: 21708004Scopus ID: 2-s2.0-79959571469OAI: oai:DiVA.org:oru-27559DiVA, id: diva2:605192
Note

Funding Agencies:

Royal Physiographic Society in Lund (Nilsson-Ehle Foundation)  

Royal Society of Arts and Sciences in Gothenburg 

Available from: 2013-02-13 Created: 2013-02-13 Last updated: 2018-03-02Bibliographically 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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