Patterns of specific genomic alterations associated with poor prognosis inhigh-grade renal cell carcinomas

A series of 13 sporadic renal cell carcinomas was analyzed for the specific chromosome rearrangements after serial xenografting into immunodeficient m ice. Seven tumors displayed genetic traits of the conventional subtype and 5 showed genetic features of the papillary subtype. In all the xenografted conventional tumors, we observed loss of 3p, as well as loss of the 9p21 re gion and of the long arm of chromosome 14, both considered as markers of a poor prognosis. In the xenografted papillary tumors, a duplication of chrom osome arm 8q was observed concomitant with the duplication of the 7q31 regi on. The association of the 7q31 and 8q22 similar to qter duplicated regions was also observed for one conventional tumor. The latency of tumor take wa s found to be reduced and the median time to passage statistically shorter for all tumors which presented the associated duplication of the 7q31 and 8 q22 similar to qter regions. The proto-oncogene NOV (nephroblastoma overexp ressed gene) maps to 8q24.1 and is overexpressed in some Wilms tumors. It c ould be an interesting candidate gene, since its level of expression and re lease in the culture medium was found to be increased in all of the fast gr owing tumors analyzed. (C) 2001 Elsevier Science Inc. All rights reserved.