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Combined LOH/CGH analysis proves the existence of interstitial 3p deletions in renal cell carcinoma

Oncogene volume 19, pages 1392–1399 (2000)Cite this article

Abstract

We have recently developed an allele titration assay (ATA) to assess the sensitivity and influence of normal cell admixture in loss of heterozygosity (LOH) studies based on CA-repeat. The assay showed that these studies are biased by the size-dependent differential sensitivity of allele detection. Based on these data, we have set up new criteria for evaluation of LOH. By combining these new rules with comparative genome hybridization (CGH) we have shown the presence of interstitial deletions in renal cell carcinoma (RCC) biopsies and cell lines. At least three out of 11 analysed RCC cell lines and three out of 37 biopsies contain interstitial deletions on chromosome 3. Our study suggests the presence of several regions on human chromosome 3 that might contribute to tumor development by their loss: (i) 3p25-p26, around the VHL gene (D3S1317); (ii) 3p21.3-p22 (between D3S1260 and D3S1611); (iii) 3p21.2 (around D3S1235 and D3S1289); (iv) 3p13-p14 (around D3S1312 and D3S1285). For the first time, AP20 region (3p21.3-p22) was carefully tested for LOH in RCC. It was found that the AP20 region is the most frequently affected area. Our data also suggest that another tumor suppressor gene is located near the VHL gene in 3p25-p26.

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Acknowledgements

This work was supported by research grants from Swedish Cancer Society, Karolinska Institute and Ã…ke Wiberg foundation. M Kost-Alimova and J Liu were recipients of fellowships from the Concern Foundation in Los Angeles and the Cancer Research Institute in New York. A Alimov was a recipient of a fellowship from Wenner Gren foundation.

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Authors and Affiliations

  1. Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, 171 77, Sweden

    Andrei Alimov, Maria Kost-Alimova, Jian Liu, Stefan Imreh, George Klein & Eugene R Zabarovsky

  2. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 117 984, Russia

    Andrei Alimov, Maria Kost-Alimova & Eugene R Zabarovsky

  3. Department of Urology, Karolinska Hospital, Stockholm, 171 76, Sweden

    Chunde Li & Ulf Bergerheim

  4. Center for Genomics Research, Karolinska Institute, Stockholm, 171 77, Sweden

    Eugene R Zabarovsky

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  1. Andrei Alimov
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Alimov, A., Kost-Alimova, M., Liu, J. et al. Combined LOH/CGH analysis proves the existence of interstitial 3p deletions in renal cell carcinoma. Oncogene 19, 1392–1399 (2000). https://doi.org/10.1038/sj.onc.1203449

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