title: 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.
authors.affiliation: 1. Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD, USA;
authors.forename: Stephanie
authors.initials: S
authors.lastname: Roessler
authors.affiliation: 1. Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD, USA; ; 2. Liver Cancer Institute, Fudan University, Shanghai, China;
authors.forename: Guoling
authors.initials: G
authors.lastname: Lin
authors.affiliation: 1. Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD, USA;
authors.forename: Marshonna
authors.initials: M
authors.lastname: Forgues
authors.affiliation: 1. Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD, USA;
authors.forename: Anuradha
authors.initials: A
authors.lastname: Budhu
authors.affiliation: 3. Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA;
authors.forename: Shelley
authors.initials: S
authors.lastname: Hoover
authors.affiliation: 3. Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA;
authors.forename: R Mark
authors.initials: RM
authors.lastname: Simpson
authors.affiliation: 4. Laboratory of Molecular Technology, NCI-Frederick, SAIC-Frederick, Frederick, MD 21701, USA;
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wu
authors.affiliation: 5. Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: 2. Liver Cancer Institute, Fudan University, Shanghai, China;
authors.forename: Lun-Xiu
authors.initials: LX
authors.lastname: Qin
authors.affiliation: 2. Liver Cancer Institute, Fudan University, Shanghai, China;
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
authors.affiliation: 2. Liver Cancer Institute, Fudan University, Shanghai, China;
authors.forename: Qing-Hai
authors.initials: QH
authors.lastname: Ye
authors.affiliation: 1. Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD, USA;
authors.forename: Xin Wei
authors.initials: XW
authors.lastname: Wang
mesh_terms: D002681:China; D015179:Colorectal Neoplasms / Q000235:genetics / Q000556:secondary*; D055028:Comparative Genomic Hybridization; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D061346:Laser Capture Microdissection; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary*; D046228:Microarray Analysis; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000503:physiopathology*
keywords: Colon cancer; Liver cancer; Organ site-specific metastasis; Profiling.