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Analysis of chromosome 10 aberrations in rat endometrial cancer: evidence for a tumor suppressor locus distal to Tp53
CMB-Genetics, Lundberg Laboratory, Göteborg University, SE 40530 Gothenhurg, Sweden.
Högskolan i Skövde, Institutionen för vård och natur.
CMB-Genetics, Lundberg Laboratory, Göteborg University, SE 40530 Gothenhurg, Sweden / Division of Medicine/Oncology, Stanford School of Medicine, Stanford, CA 94305, United States.
Institute of Biomedicine, Department of Microbiology and Immunology, Göteborg University, SE 40530 Gothenburg, Sweden.
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2007 (Engelska)Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 120, nr 7, s. 1472-1481Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

We have recently shown in the BDII rat model of human endometrial adenocarcinoma (EAC), rat chromosome 10 (RNO10) is frequently involved in chromosomal aberrations. In the present study, we investigated the association between RNO10 deletions, allelic imbalance (AI) at RNO10q24 and Tp53 mutation in 27 rat EAC tumors. We detected chromosomal breakage accompanied by loss of proximal and/or gain of distal parts of RNO10 in approximately 2/3 of the tumors. This finding is suggestive of a tumor suppressor activity encoded from the proximal RNO10. Given the fact that Tp53 is located at RNO10q24-q25, we then performed Tp53 mutation analysis. However, we could not find a strong correlation between AI/deletions at RNO10q24 and Tp53 mutation. Instead, the observed patterns for AI, chromosomal breaks and deletions suggest that major selection was directed against a region located close to, but distal of Tp53. In different human malignancies a similar situation of AI at chromosome band 17p13.3 (HSA17p13.3) unassociated with TP53 mutation has been observed. Although RNO10 is largely homologous to HSA17, the conservation with respect to gene order among them is not extensive. We utilized publicly available draft DNA sequences to study intrachromosomal rearrangement during the divergence between HSA17 and RNO10. By using reciprocal comparison of rat and human genome data, we could substantially narrow down the candidate tumor suppressor region in rat from 3 Mb to a chromosomal segment of about 0.5 Mb in size. These results provide scientific groundwork for identification of the putative tumor suppressor gene(s) at 17p13.3 in human tumors

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John Wiley & Sons, 2007. Vol. 120, nr 7, s. 1472-1481
Nyckelord [en]
BDII, endometrial adenocarcinoma, RNO10, 17p13.3, allelic imbalance, Tp53 mutation, tumor suppressor gene
Identifikatorer
URN: urn:nbn:se:his:diva-2027DOI: 10.1002/ijc.22533ISI: 000244610700013PubMedID: 17245700Scopus ID: 2-s2.0-33847687821OAI: oai:DiVA.org:his-2027DiVA, id: diva2:32303
Tillgänglig från: 2008-05-07 Skapad: 2008-05-07 Senast uppdaterad: 2017-12-12Bibliografiskt granskad

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Karlsson, SandraKlinga-Levan, Karin

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