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Mapping of the 7q31 subregion common to the small chromosome 7 derivatives from two sporadic papillary renal cell carcinomas: increased copy number and overexpression of the MET proto-oncogene

Oncogene volume 19, pages 754–761 (2000)Cite this article

Abstract

Molecular cytogenetic analysis of several sporadic papillary renal cell carcinomas and of their xenografts in immunodeficient mice had previously allowed us to delimit a minimal overrepresented region of chromosome 7 shared by all of them to band 7q31. We have refined the location of the overlapping region to the junction of the subbands 7q31.2 and 7q31.3 by reverse painting with two differently labelled probes prepared from the small chromosome 7 derivatives microdissected from the cells of two distinct tumours. This small region was shown to contain the MET proto-oncogene, present at three to four copies per cell as determined by Southern blot analysis. The increased copy number of the MET gene was found to be associated with its overexpression at the mRNA level. However, no change in MET copy number or expression level was observed in the cells from two xenografted tumours serially transplanted into immunodeficient mice, as compared to those from the corresponding initial tumours. Our results indicate that expression of the MET proto-oncogene above a critical threshold is required for the maintenance of the tumorigenic phenotype of at least some papillary renal cell carcinomas, but does not further increase during tumour progression.

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Acknowledgements

We are very grateful to Drs Berton Zbar (Frederick, MD, USA) and Olivier Brison (Villejuif) for helpful comments and critical reading of the manuscript. We thank Dr Horacio G Suárez (Villejuif) for the pmetD, pmetH and pHOS-1 probes, Dr Francis Collins and Michael R Erdos (Bethesda, MD, USA) for the H2.3A probe, Drs Gordon Peters and Clive Dickson (London) for the BK4 probe, Dr Walter Birchmeier and Martin Sachs (Berlin) for plasmid pBAT-SFtag containing an HGF cDNA fragment probe and Dr Serge Alonso (Paris) for plasmid pAL41. This work was supported by the Centre National de la Recherche Scientifique, the Ligue Nationale Contre le Cancer (Comité du Val de Marne) and the Institut Gustave Roussy. L. Glukhova was the recipient of a fellowship from the Association pour la Recherche sur le Cancer.

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Authors and Affiliations

  1. Laboratoire de Cytogénétique et Génétique Oncologiques, UMR 1599, PR2, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif cedex, 94805, France

    Liubov Glukhova, Didier Fauvet, Gisèle Danglot, Alain Bernheim & Anne-Françoise Goguel

  2. Laboratoire de Génétique Oncologique, Unité Mixte de Recherche 1599 du Centre National de la Recherche Scientifique, Institut Gustave Roussy,, 94805, Villejuif cedex, France

    Christian Lavialle

  3. Institut fur Humangenetik und Anthropologie, Jena, D-07740, Germany

    Ilse Chudoba

  4. Unité d'Immunothérapie, Institut Gustave Roussy, 94805, Villejuif cedex, France

    Eric Angevin

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  1. Liubov Glukhova
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Glukhova, L., Lavialle, C., Fauvet, D. et al. Mapping of the 7q31 subregion common to the small chromosome 7 derivatives from two sporadic papillary renal cell carcinomas: increased copy number and overexpression of the MET proto-oncogene. Oncogene 19, 754–761 (2000). https://doi.org/10.1038/sj.onc.1203397

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