Integrative genomic and transcriptomic characterization of matched primary and metastatic liver and colorectal carcinoma

Abstract

Metastasis is the main cause of cancer mortality but its process remains poorly understood and thus hampers more effective treatment and improved cancer prognosis. To search for metastasis driver genes responsible for tumor spread, we integrated genomic and transcriptomic profiles of 61 matched primary tumors and distant metastases of liver or colorectal carcinoma isolated by laser-capture microdissection and assayed by array-based technologies. We found that primary tumor lesions and their matched distant metastases were largely similar at the genomic and transcriptomic levels, but substantial differences could be found between primary tumors with or without accompanying metastases. Interestingly, metastasis genes were principally tumor type and organ site-specific. Despite distinct pathway enrichment, different metastasis gene sets shared common prognostic capacity and were predictive of hepatocellular carcinoma survival in an independent cohort. Thus, the metastatic propensity is inherent to the primary tumor and the lack of general metastasis genes necessitates the development of specific treatment modalities.