Evaluation of the oncogenic potential of genes within the 1q23 amplicon

Comparative genomic hybridization identified amplification of 1q23 to be associated with liposarcomas. Further analyses of 1q23 narrowed down the candidate “driver” genes to two; DUSP12 (encoding a dual-specificity phosphatase) and ATF6 (a transcription factor of the unfolded protein response). We propose to assess the specific consequences of DUSP12/ATF6 over-expression by creating stable inducible cell lines as models of 1q23 amplification. The consequences of specific DUSP12 or ATF6 over-expression on MAP Kinase and other cancer-relevant signaling pathways will be evaluated. Identification of these pathways may expose novel vulnerabilities that can be exploited in the treatment of sarcomas by accelerating translational therapeutics.