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Genomic Alterations in Experimental Endometrial Adenocarcinoma
University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
2012 (English)Licentiate thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro University , 2012. , 23 p.
Series
Licentiate Thesis in Biomedicine, 8
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
URN: urn:nbn:se:his:diva-7419ISBN: 978-91-637-1624-9 OAI: oai:DiVA.org:his-7419DiVA: diva2:611662
Supervisors
Available from: 2013-03-18 Created: 2013-03-18 Last updated: 2013-08-22Bibliographically approved
List of papers
1. SKY analysis revealed recurrent numerical and structural chromosome changes in BDII rat endometrial carcinomas
Open this publication in new window or tab >>SKY analysis revealed recurrent numerical and structural chromosome changes in BDII rat endometrial carcinomas
2011 (English)In: Cancer Cell International, ISSN 1475-2867, Vol. 11, 20- p.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
Keyword
SKY, BDII rat, endometrial carcinoma
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-5536 (URN)10.1186/1475-2867-11-20 (DOI)000293340700001 ()2-s2.0-79959571469 (Scopus ID)
Available from: 2012-03-19 Created: 2012-03-01 Last updated: 2013-03-18Bibliographically approved
2. The impact of the genetic background on the genome make-up of tumor cells
Open this publication in new window or tab >>The impact of the genetic background on the genome make-up of tumor cells
2012 (English)In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 51, no 5, 438-446 p.Article 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
Wiley-Blackwell, 2012
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-5665 (URN)10.1002/gcc.21929 (DOI)000301118100003 ()
Available from: 2012-04-02 Created: 2012-04-02 Last updated: 2013-03-18Bibliographically approved

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Citation style
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