中央研究院 資訊科學研究所

Cancer is a genetic disease of somatic cell with accumulated mutations in cancer genome during tumorigenic progression.  Cancer cells with gain of function driver mutations commonly confer proliferation and mobility advantages over surrounding normal cells resulted in tumor outgrowth and metastasis.  Driver mutations in cancer cells constitutively activated oncogenic signaling pathway lead to development of cancerous phenotypes and become suitable target for cancer therapy.  For instance, driver mutations of EGFR, a tyrosine kinase, were commonly identified in cancer cells of lung cancer patients.  The constitutive active EGFR oncogenic signaling resulted in addicted and oncogenic cancer cells is a clinically promising therapeutic target of lung cancer patients to be treated with tyrosine kinase inhibitor such as Gefitinib or Erlotinib.

We applied integrated genomic approaches including comprehensive analysis of copy number alterations (CNAs) of cancer genomes and aberrant gene expression in cancer cells with high density microarrays.  We uncovered novel driver genes resided in CNA regions, revealed the tumorigenic mechanisms in vitro and in vivo, and explored the therapeutic inhibitors for potential cancer therapy.  Comprehensive and integrated analysis of cancer genomes especially human hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC) further allowed us to construct open-accessed databases to facilitate identification of driver cancer genes for translational applications.