Blog
About

14
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Whole-genome landscapes of major melanoma subtypes

      , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

      Nature

      Springer Nature

      Read this article at

      ScienceOpenPublisherPubMed
      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

          The first large, high-coverage whole-genome sequencing study of melanomas from cutaneous, acral and mucosal sites.

          Related collections

          Most cited references 26

          • Record: found
          • Abstract: found
          • Article: not found

          Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines.

          The gradual loss of DNA from the ends of telomeres has been implicated in the control of cellular proliferative potential. Telomerase is an enzyme that restores telomeric DNA sequences, and expression of its activity was thought to be essential for the immortalization of human cells, both in vitro and in tumor progression in vivo. Telomerase activity has been detected in 50-100% of tumors of different types, but not in most normal adult somatic tissues. It has also been detected in about 70% of human cell lines immortalized in vitro and in all tumor-derived cell lines examined to date. It has previously been shown that in vitro immortalized telomerase-negative cell lines acquire very long and heterogeneous telomeres in association with immortalization presumably via one or more novel telomere-lengthening mechanisms that we refer to as ALT (alternative lengthening of telomeres). Here we report evidence for the presence of ALT in a subset of tumor-derived cell lines and tumors. The maintenance of telomeres by a mechanism other than telomerase, even in a minority of cancers, has major implications for therapeutic uses of telomerase inhibitors.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Exome sequencing identifies GRIN2A as frequently mutated in melanoma.

            The incidence of melanoma is increasing more than any other cancer, and knowledge of its genetic alterations is limited. To systematically analyze such alterations, we performed whole-exome sequencing of 14 matched normal and metastatic tumor DNAs. Using stringent criteria, we identified 68 genes that appeared to be somatically mutated at elevated frequency, many of which are not known to be genetically altered in tumors. Most importantly, we discovered that TRRAP harbored a recurrent mutation that clustered in one position (p. Ser722Phe) in 6 out of 167 affected individuals (∼4%), as well as a previously unidentified gene, GRIN2A, which was mutated in 33% of melanoma samples. The nature, pattern and functional evaluation of the TRRAP recurrent mutation suggest that TRRAP functions as an oncogene. Our study provides, to our knowledge, the most comprehensive map of genetic alterations in melanoma to date and suggests that the glutamate signaling pathway is involved in this disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              In silico prescription of anticancer drugs to cohorts of 28 tumor types reveals targeting opportunities.

              Large efforts dedicated to detect somatic alterations across tumor genomes/exomes are expected to produce significant improvements in precision cancer medicine. However, high inter-tumor heterogeneity is a major obstacle to developing and applying therapeutic targeted agents to treat most cancer patients. Here, we offer a comprehensive assessment of the scope of targeted therapeutic agents in a large pan-cancer cohort. We developed an in silico prescription strategy based on identification of the driver alterations in each tumor and their druggability options. Although relatively few tumors are tractable by approved agents following clinical guidelines (5.9%), up to 40.2% could benefit from different repurposing options, and up to 73.3% considering treatments currently under clinical investigation. We also identified 80 therapeutically targetable cancer genes.
                Bookmark

                Author and article information

                Journal
                Nature
                Nature
                Springer Nature
                0028-0836
                1476-4687
                May 3 2017
                May 3 2017
                :
                :
                Article
                10.1038/nature22071
                28467829
                © 2017
                Product

                Comments

                Comment on this article