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

Molecular cytogenetic analysis of several sporadic papillary renal cell car cinomas and of their xenografts in immunodeficient mice had previously allo wed us to delimit a minimal overrepresented region of chromosome 7 shaped b y 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 painti ng with two differently labelled probes prepared from the small chromosome 7 derivatives microdissected from the cells of two distinct tumours, This s mall region was shown to contain the MET proto-oncogene, present at three t o four copies per cell as determined by Southern blot analysis, The increas ed copy number of the MET gene was found to be associated with its overexpr ession at the mRNA level. However, no change in MET copy number or expressi on level was observed in the cells from two xenografted tumours serially tr ansplanted into immunodeficient mice, as compared to those from the corresp onding initial tumours. Our results indicate that expression of the MET pro to-oncogene above a critical threshold is required for the maintenance of t he tumorigenic phenotype of at least some papillary renal cell carcinomas, but does not further increase during tumour progression.