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      The Role of Aneuploidy in Cancer Evolution

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          Abstract

          Chromosomal aberrations during cell division represent one of the first recognized features of human cancer cells, and modern detection methods have revealed the pervasiveness of aneuploidy in cancer. The ongoing karyotypic changes brought about by chromosomal instability (CIN) contribute to tumor heterogeneity, drug resistance, and treatment failure. Whole-chromosome and segmental aneuploidies resulting from CIN have been proposed to allow “macroevolutionary” leaps that may contribute to profound phenotypic change. In this review, we will outline evidence indicating that aneuploidy and CIN contribute to cancer evolution.

          Abstract

          Chromosome segregation errors during cell division are some of the first recognized features of cancer cells. The resulting karyotypic changes contribute to tumor heterogeneity, drug resistance, and treatment failure.

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          Most cited references78

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

          J. Gao, B. A. Aksoy, U Dogrusoz … (2015)
          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.
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            Genetic instabilities in human cancers.

            C Lengauer, K Kinzler, B Vogelstein (1998)
            Whether and how human tumours are genetically unstable has been debated for decades. There is now evidence that most cancers may indeed be genetically unstable, but that the instability exists at two distinct levels. In a small subset of tumours, the instability is observed at the nucleotide level and results in base substitutions or deletions or insertions of a few nucleotides. In most other cancers, the instability is observed at the chromosome level, resulting in losses and gains of whole chromosomes or large portions thereof. Recognition and comparison of these instabilities are leading to new insights into tumour pathogenesis.
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              The spindle-assembly checkpoint in space and time.

              Andrea Musacchio, Edward Salmon (2007)
              In eukaryotes, the spindle-assembly checkpoint (SAC) is a ubiquitous safety device that ensures the fidelity of chromosome segregation in mitosis. The SAC prevents chromosome mis-segregation and aneuploidy, and its dysfunction is implicated in tumorigenesis. Recent molecular analyses have begun to shed light on the complex interaction of the checkpoint proteins with kinetochores--structures that mediate the binding of spindle microtubules to chromosomes in mitosis. These studies are finally starting to reveal the mechanisms of checkpoint activation and silencing during mitotic progression.
              Article 0 comments Cited 687 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cold Spring Harb Perspect Med
                Journal ID (iso-abbrev): Cold Spring Harb Perspect Med
                Journal ID (publisher-id): cshperspectmed
                Journal ID (hwp): cshperspectmed
                Title: Cold Spring Harbor Perspectives in Medicine
                Publisher: Cold Spring Harbor Laboratory Press
                ISSN (Electronic): 2157-1422
                Publication date (Print): January 2017
                Volume: 7
                Issue: 1
                Electronic Location Identifier: a028373
                Affiliations
                [1 ]Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, Lincoln’s Inn Fields Laboratories, London WC2A 3LY, United Kingdom
                [2 ]CRUK Lung Cancer Centre of Excellence/UCL Cancer Institute, London WC1E 6BT, United Kingdom
                Author notes
                Article
                Accession ID: PMC5204330 Pmcid ID: PMC5204330 Pmc-uid ID: 5204330 Publisher ID: a028373
                DOI: 10.1101/cshperspect.a028373
                PMC ID: 5204330
                PubMed ID: 28049655
                SO-VID: 419a6083-9b77-459a-a5a2-1f806c7df237
                Copyright © Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved
                History
                Page count
                Pages: 17
                Categories
                Subject: 118
                Subject: Perspectives

                Data availability:

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