Identification and Validation of Oncogenes in Liver Cancer Using an Integrative Oncogenomic Approach

Abstract

The heterogeneity and instability of human tumors hamper straightforward identification of cancer-causing mutations through genomic approaches alone. Herein we describe a mouse model of liver cancer initiated from progenitor cells harboring defined cancer-predisposing lesions. Genome-wide analyses of tumors in this mouse model and in human hepatocellular carcinomas revealed a recurrent amplification at mouse chromosome 9qA1, the syntenic region of human chromosome 11q22. Gene-expression analyses delineated cIAP1, a known inhibitor of apoptosis, and Yap, a transcription factor, as candidate oncogenes in the amplicon. In the genetic context of their amplification, both cIAP1 and Yap accelerate..