期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 11, 页码 4079-4084出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0810803106
关键词
canonical distributions; combinatorial regulation; correlation vectors
资金
- Irish Research Council for Science Engineering and Technology
- Science Foundation Ireland Research Frontiers
- European Union Marie Curie Research [MRTN-CT-2003-504712]
Although cancer types differ substantially, many cancers share common gene expression signatures. Consistent with this observation, we find convergent and representative distributions and correlation vectors that are distinct in cancer and noncancer ensembles. These differences originate in many genes, but comparatively few genes account for the major differences. We identify genes with different combinatorial regulation in cancer and noncancer as indicated by significant differences in their correlation vectors. Among the identified genes are many established oncogenes and apoptotic genes (such as members of the Bcl-2, the MAPK, and the Ras families) and new candidate oncogenes. Our findings expand and complement the tumorigenic role of up and down regulation of these genes by emphasizing cancer-specific changes in their couplings and correlation patterns at genome-wide level that are independent from their mean levels of expression in cancer cells. Given the central role of these genes in defining the cancerous state it may be worth investigating them and the differences in their combinatorial regulation for developing wide-spectrum anticancer drugs.
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