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Recurrent Chromosome 10 Aberrations and Tp53 Mutations in Rat Endometrial Adenocarcinomas

  • Carola Nordlander
  • Emma Samuelson
  • Karin Klinga-Levan
  • Afrouz Behboudi
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)

Summary

Human genetic heterogeneity and differences in the environment and life style make analysis of complex diseases such as cancer difficult. By using inbred animal strains, the genetic variability can be minimized and the environmental factors can be reasonably controlled. Endometrial adenocarcinoma (EAC) is the most common gynecologic malignancy, ranking fourth in incidence among tumors in women. The inbred BDII rat strain is genetically prone to spontaneously develop hormone-related EAC, and can be used as a tool to investigate and characterize genetic changes in this tumor type. In the present project, BDII females were crossed to males from two nonsusceptible rat strains and F1, F2, and backcross progeny were produced. Genetic and molecular genetic analysis of tumors showed that rat chromosome 10 (RNO10) was frequently involved in genetic changes. Our data indicate that often there was loss of chromosomal material in the proximal to middle part of the chromosome followed by gains in distal RNO10. This suggested that there is a tumor suppressor gene(s) in the proximal to middle part of RNO10 and an oncogene(s) in the distal part of the chromosome with potential significance in EAC development. The Tp53 gene, located at band RNO10q24-q25, was a strong candidate target for the observed aberrations affecting the middle part of the chromosome. However, our Tp53 gene mutation analyses suggested that a second gene situated very close to Tp53 might be the main target for the observed pattern of genetic changes.

Keywords

Comparative Genome Hybridization Endometrial Carcinoma Tp53 Mutation Tp53 Gene Allelic Imbalance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Boyd J (1996) Molecular biology in the clinicopathologic assessment of endometrial carcinoma subtypes. Gynecologic Oncology 61:163–165.PubMedCrossRefGoogle Scholar
  2. 2.
    Lax SF (2004) Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification. Virchows Archiv 444(3):213–223.PubMedCrossRefGoogle Scholar
  3. 3.
    Kaspareit-Rittinghausen J, Deerberg F, Rapp K (1987) Mortality and incidence of spontaneous neoplasms in BDII/Han rats. Zeitschrift für Versuchstierkunde 30:209–216.PubMedGoogle Scholar
  4. 4.
    Deerberg F, Kaspareit J (1987) Endometrial carcinoma in BDII/Han rats: model of a spontaneous hormone-dependent tumor. J Natl Cancer Inst 78:1245–1251.PubMedGoogle Scholar
  5. 5.
    Roshani L, Wedekind D, Szpirer J, et al. (2001) Genetic identification of multiple susceptibility genes involved in the development of endometrial carcinoma in a rat model. Int J Cancer 94:795–799.PubMedCrossRefGoogle Scholar
  6. 6.
    Roshani L, Mallon P, Sjostrand E, et al. (2005) Genetic analysis of susceptibility to endometrial adenocarcinoma in the BDII rat model. Cancer Genet Cytogenet 158:137–141.PubMedCrossRefGoogle Scholar
  7. 7.
    Helou K, Walentinsson A, Beckmann B, et al. (2001) Analysis of genetic changes in rat endometrial carcinomas by means of comparative genome hybridization. Cancer Genet Cytogenet 127:118–127.PubMedCrossRefGoogle Scholar
  8. 8.
    Hamta A, Adamovic T, Helou K, et al. (2005) Cytogenetic aberrations in spontaneous endometrial adenocarcinomas in the BDII rat model as revealed by chromosome banding and comparative genome hybridization. Cancer Genet Cytogenet 159:123–128.PubMedCrossRefGoogle Scholar
  9. 9.
    Behboudi A, Levan G, Hedrich HJ, et al. (2001) High-density marker loss of heterozygosity analysis of rat chromosome 10 in endometrial adenocarcinoma. Gene Chromosome Cancer 32:330–341.CrossRefGoogle Scholar
  10. 10.
    Nordlander C, Behboudi A, Levan G, et al. (2005) Allelic imbalance on chromosome 10 in rat endometrial adenocarcinomas. Cancer Genet Cytogenet 156:158–166.PubMedCrossRefGoogle Scholar
  11. 11.
    Nordlander C, Karlsson S, Karlsson Å, et al. (2007) Analysis of chromosome 10 aberrations in rat endometrial cancer – evidence for a tumor suppressor locus distal to Tp53. Int J Cancer 120:1472–1481.PubMedCrossRefGoogle Scholar
  12. 12.
    Coles C, Thompson AM, Elder PA, et al. (1990) Evidence implicating at least two genes on chromosome 17p in breast carcinogenesis. Lancet 336:761–763.PubMedCrossRefGoogle Scholar
  13. 13.
    Jung HL, Wang KC, Kim SK, et al. (2004) Loss of heterozygosity analysis of chromosome 17p13.1–13.3 and its correlation with clinical outcome in medulloblastomas. J Neuro Oncol 67:41–46.CrossRefGoogle Scholar
  14. 14.
    Konishi H, Sugiyama M, Mizuno K, et al. (2003) Detailed characterization of a homozygously deleted region corresponding to a candidate tumor suppressor locus at distal 17p13.3 in human lung cancer. Oncogene 22:1892–1905.PubMedCrossRefGoogle Scholar
  15. 15.
    Roncuzzi L, Brognara I, Baiocchi D, et al. (2005) Loss of heterozygosity at 17p13.3-ter, distal to TP53, correlates with negative hormonal phenotype in sporadic breast cancer. Oncol Rep 14:471–474.PubMedGoogle Scholar
  16. 16.
    Sarkar C, Chattopadhyay P, Ralte AM, et al. (2003) Loss of heterozygosity of a locus in the chromosomal region 17p13.3 is associated with increased cell proliferation in astrocytic tumors. Cancer Genet Cytogenet 144:156–164.PubMedCrossRefGoogle Scholar
  17. 17.
    Zhao X, He M, Wan D, et al. (2003) The minimum LOH region defined on chromosome 17p13.3 in human hepatocellular carcinoma with gene content analysis. Cancer lett 190:221–232.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Carola Nordlander
    • 1
  • Emma Samuelson
    • 2
  • Karin Klinga-Levan
  • Afrouz Behboudi
  1. 1.Department of Cellular and Molecular Biology-GeneticsLundberg InstituteGöteborgSweden
  2. 2.Sahlgrenska Academy Department of Clinical GeneticsGöteborg UniversityGöteborgSweden

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