Blog
About

78
views
0
recommends
+1 Recommend
0 collections
    10
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Emerging landscape of oncogenic signatures across human cancers

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Cancer therapy is challenged by the diversity of molecular implementations of oncogenic processes and by the resulting variation in therapeutic responses. Projects such as The Cancer Genome Atlas (TCGA) provide molecular tumor maps in unprecedented detail. The interpretation of these maps remains a major challenge. Here we distilled thousands of genetic and epigenetic features altered in cancers to ~500 selected functional events (SFEs). Using this simplified description, we derived a hierarchical classification of 3,299 TCGA tumors from 12 cancer types. The top classes are dominated by either mutations (M class) or copy number changes (C class). This distinction is clearest at the extremes of genomic instability, indicating the presence of different oncogenic processes. The full hierarchy shows functional event patterns characteristic of multiple cross-tissue groups of tumors, termed oncogenic signature classes. Targetable functional events in a tumor class are suggestive of class-specific combination therapy. These results may assist in the definition of clinical trials to match actionable oncogenic signatures with personalized therapies.

          Related collections

          Most cited references 25

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Modularity and community structure in networks

           M. Newman (2006)
          Many networks of interest in the sciences, including a variety of social and biological networks, are found to divide naturally into communities or modules. The problem of detecting and characterizing this community structure has attracted considerable recent attention. One of the most sensitive detection methods is optimization of the quality function known as "modularity" over the possible divisions of a network, but direct application of this method using, for instance, simulated annealing is computationally costly. Here we show that the modularity can be reformulated in terms of the eigenvectors of a new characteristic matrix for the network, which we call the modularity matrix, and that this reformulation leads to a spectral algorithm for community detection that returns results of better quality than competing methods in noticeably shorter running times. We demonstrate the algorithm with applications to several network data sets.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Patterns of somatic mutation in human cancer genomes.

            Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Resolution limit in community detection

              Detecting community structure is fundamental to clarify the link between structure and function in complex networks and is used for practical applications in many disciplines. A successful method relies on the optimization of a quantity called modularity [Newman and Girvan, Phys. Rev. E 69, 026113 (2004)], which is a quality index of a partition of a network into communities. We find that modularity optimization may fail to identify modules smaller than a scale which depends on the total number L of links of the network and on the degree of interconnectedness of the modules, even in cases where modules are unambiguously defined. The probability that a module conceals well-defined substructures is the highest if the number of links internal to the module is of the order of \sqrt{2L} or smaller. We discuss the practical consequences of this result by analyzing partitions obtained through modularity optimization in artificial and real networks.
                Bookmark

                Author and article information

                Journal
                9216904
                2419
                Nat Genet
                Nat. Genet.
                Nature genetics
                1061-4036
                1546-1718
                24 April 2014
                October 2013
                26 March 2015
                : 45
                : 10
                : 1127-1133
                Affiliations
                Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
                Author notes
                Correspondence should be addressed to G.C., N.S. or C.S. ( pancan@ 123456cbio.mskcc.org )
                Article
                NIHMS550190
                10.1038/ng.2762
                4320046
                24071851
                © 2013 Nature America, Inc. All rights reserved.

                This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

                Categories
                Article

                Genetics

                Comments

                Comment on this article