4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Actionable Potentials of Less Frequently Mutated Genes in Colorectal Cancer and Their Roles in Precision Medicine

      review-article

      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

          Global statistics have placed colorectal cancer (CRC) as the third most frequently diagnosed cancer and the fourth principal cause of cancer-related deaths worldwide. Improving survival for CRC is as important as early detection. Personalized medicine is important in maximizing an individual’s treatment success and minimizing the risk of adverse reactions. Approaches in achieving personalized therapy in CRC have included analyses of specific genes with its clinical implications. Tumour genotyping via next-generation sequencing has become a standard practice to guide clinicians into predicting tumor behaviour, disease prognosis, and treatment response. Nevertheless, better prognostic markers are necessary to further stratify patients for personalized treatment plans. The discovery of new markers remains indispensable in providing the most effective chemotherapy in order to improve the outcomes of treatment and survival in CRC patients. This review aims to compile and discuss newly discovered, less frequently mutated genes in CRC. We also discuss how these mutations are being used to assist therapeutic decisions and their potential prospective clinical utilities. In addition, we will summarize the importance of profiling the large genomic rearrangements, gene amplification, and large deletions and how these alterations may assist in determining the best treatment option for CRC patients.

          Related collections

          Most cited references100

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

          Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.

          The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation.

            FBW7 (F-box and WD repeat domain-containing 7) is the substrate recognition component of an evolutionary conserved SCF (complex of SKP1, CUL1 and F-box protein)-type ubiquitin ligase. SCF(FBW7) degrades several proto-oncogenes that function in cellular growth and division pathways, including MYC, cyclin E, Notch and JUN. FBW7 is also a tumour suppressor, the regulatory network of which is perturbed in many human malignancies. Numerous cancer-associated mutations in FBW7 and its substrates have been identified, and loss of FBW7 function causes chromosomal instability and tumorigenesis. This Review focuses on structural and functional aspects of FBW7 and its role in the development of cancer.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              High-throughput oncogene mutation profiling in human cancer.

              Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention.
                Bookmark

                Author and article information

                Journal
                Biomolecules
                Biomolecules
                biomolecules
                Biomolecules
                MDPI
                2218-273X
                20 March 2020
                March 2020
                : 10
                : 3
                : 476
                Affiliations
                UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; ryia.yunos@ 123456ppukm.ukm.edu.my (R.I.M.Y.); francistieng@ 123456yahoo.com.my (F.Y.F.T.); nadiah.abu@ 123456ppukm.ukm.edu.my (N.A.)
                Author notes
                [* ]Correspondence: syakima@ 123456ppukm.ukm.edu.my (N.S.A.M.); rahmanj@ 123456ppukm.ukm.edu.my (R.J.); Tel.: +60-3-91459073 (N.S.A.M.); +60-3-91459000 (R.J.)
                Author information
                https://orcid.org/0000-0001-6914-2224
                https://orcid.org/0000-0002-2504-3934
                Article
                biomolecules-10-00476
                10.3390/biom10030476
                7175115
                32245111
                e9041f4e-3c78-4847-bc26-3be43f403b7a
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 February 2020
                : 13 March 2020
                Categories
                Review

                colorectal cancer,less frequently mutated genes,chemoresistance,precision medicine,treatment response,actionable mutations

                Comments

                Comment on this article