Reprofiling Metastatic Samples for Chromosome 9p and 14q Aberrations as a Strategy to Overcome XXXX Heterogeneity in @entity1358 .

@entity1 @entity10793 @entity7738 @entity5 @entity2282 @entity1358 @entity3 @entity393
UNASSIGNED: Losses of chromosomes 9p and 14q are associated with worse outcomes in @entity1 affected by @entity1358 ( @entity1358 ) and are helpful for prognostic risk stratification. Both chromosomal loci harbor several hot-spot molecular pathways suitable for targeted therapeutic interventions. Intratumor heterogeneity may foster @entity5 adaptation and therapeutic failure. We sought to investigate the presence of losses of the hot spots of chromosomal loci 9p and 14q in primary clear-cell @entity1358 and matched metastatic tissues. @entity2282 and @entity10793 were performed on 7 cases of clear-cell @entity1358 with hematogenous tissue @entity3 . Cytogenetic fluorescence in situ hybridization analysis was performed on primary and matched metastatic tissues using specific probes mapping the 9p and the 14q loci. The @entity393 was observed in 85% of both primary clear-cell RCCs and in matched @entity3 ; 14% showed discordance between primary and matched @entity3 showing gains. The @entity393 was observed in 58% of both primary and matched @entity3 . Only 3/7 (42%) did show an equal status of @entity393 . Heterogeneity of the cytogenetic status between metastatic and primary clear-cell RCCs is observed for the @entity393 rather than chromosome 9p. The impact of chromosome 14q cytogenetic status, harboring the @entity7738 gene, a major driver for the angiogenenic switch, may drive the efficacy of targeted inhibitors, whereas the @entity393 , harboring other hot-spot genes, seems to be related to the metastatic behavior per se, without cytogenetic modulation. Reprofiling the metastatic tissue, as compared with the @entity5 , in @entity1 affected by metastatic @entity1358 could be a novel approach to overcome resistance to VEGF(Rs)-targeting agents.
