37
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Circulating biomarkers to monitor cancer progression and treatment

      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

          Tumor heterogeneity is a major challenge and the root cause of resistance to treatment. Still, the standard diagnostic approach relies on the analysis of a single tumor sample from a local or metastatic site that is obtained at a given time point. Due to intratumoral heterogeneity and selection of subpopulations in diverse lesions this will provide only a limited characterization of the makeup of the disease. On the other hand, recent developments of nucleic acid sequence analysis allows to use minimally invasive serial blood samples to assess the mutational status and altered gene expression patterns for real time monitoring in individual patients. Here, we focus on cell-free circulating tumor-specific mutant DNA and RNA (including mRNA and non-coding RNA), as well as current limitations and challenges associated with circulating nucleic acids biomarkers.

          Related collections

          Most cited references108

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

          Switching from repression to activation: microRNAs can up-regulate translation.

          AU-rich elements (AREs) and microRNA target sites are conserved sequences in messenger RNA (mRNA) 3' untranslated regions (3'UTRs) that control gene expression posttranscriptionally. Upon cell cycle arrest, the ARE in tumor necrosis factor-alpha (TNFalpha) mRNA is transformed into a translation activation signal, recruiting Argonaute (AGO) and fragile X mental retardation-related protein 1 (FXR1), factors associated with micro-ribonucleoproteins (microRNPs). We show that human microRNA miR369-3 directs association of these proteins with the AREs to activate translation. Furthermore, we document that two well-studied microRNAs-Let-7 and the synthetic microRNA miRcxcr4-likewise induce translation up-regulation of target mRNAs on cell cycle arrest, yet they repress translation in proliferating cells. Thus, activation is a common function of microRNPs on cell cycle arrest. We propose that translation regulation by microRNPs oscillates between repression and activation during the cell cycle.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Genome Remodeling in a Basal-like Breast Cancer Metastasis and Xenograft

            Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumor progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumor, a brain metastasis, and a xenograft derived from the primary tumor. The metastasis contained two de novo mutations and a large deletion not present in the primary tumor, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumor mutations, and displayed a mutation enrichment pattern that paralleled the metastasis (16 of 20 genes). Two overlapping large deletions, encompassing CTNNA1, were present in all three tumor samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared to the primary tumor suggest that secondary tumors may arise from a minority of cells within the primary.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              MicroRNAs accurately identify cancer tissue origin.

              MicroRNAs (miRNAs) belong to a class of noncoding, regulatory RNAs that is involved in oncogenesis and shows remarkable tissue specificity. Their potential for tumor classification suggests they may be used in identifying the tissue in which cancers of unknown primary origin arose, a major clinical problem. We measured miRNA expression levels in 400 paraffin-embedded and fresh-frozen samples from 22 different tumor tissues and metastases. We used miRNA microarray data of 253 samples to construct a transparent classifier based on 48 miRNAs. Two-thirds of samples were classified with high confidence, with accuracy >90%. In an independent blinded test-set of 83 samples, overall high-confidence accuracy reached 89%. Classification accuracy reached 100% for most tissue classes, including 131 metastatic samples. We further validated the utility of the miRNA biomarkers by quantitative RT-PCR using 65 additional blinded test samples. Our findings demonstrate the effectiveness of miRNAs as biomarkers for tracing the tissue of origin of cancers of unknown primary origin.
                Bookmark

                Author and article information

                Contributors
                Journal
                Comput Struct Biotechnol J
                Comput Struct Biotechnol J
                Computational and Structural Biotechnology Journal
                Research Network of Computational and Structural Biotechnology
                2001-0370
                01 June 2016
                2016
                01 June 2016
                : 14
                : 211-222
                Affiliations
                Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, 3970 Reservoir Rd, NW, Washington, DC 20007, USA
                Author notes
                [* ]Corresponding author. anton.wellstein@ 123456georgetown.edu
                Article
                S2001-0370(16)30011-3
                10.1016/j.csbj.2016.05.004
                4913179
                27358717
                68684d9b-00df-4cb7-8c80-b07f8700add6
                © 2016 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 February 2016
                : 17 May 2016
                : 18 May 2016
                Categories
                Mini Review

                cell-free dna,cell-free rna,cell-free microrna,cell-free circulating nucleic acids,circulating tumor dna,circulating mutant dna

                Comments

                Comment on this article