The Consequences of structural genomic alterations in humans: Genomic Disorders, genomic instability and cancer

Colnaghi, Rita, Carpenter, Gillian, Volker, Marcel and O'Driscoll, Mark (2011) The Consequences of structural genomic alterations in humans: Genomic Disorders, genomic instability and cancer. Seminars in Cell and Developmental Biology, 22 (8). pp. 875-885. ISSN 1084-9521

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Over the last decade or so, sophisticated technological advances in array-based genomics have firmly established the contribution of structural alterations in the human genome to a variety of complex developmental disorders, and also to diseases such as cancer. In fact, multiple ‘novel’ disorders have been identified as a direct consequence of these advances. Our understanding of the molecular events leading to the generation of these structural alterations is also expanding. Many of the models proposed to explain these complex rearrangements involve DNA breakage and the coordinated action of DNA replication, repair and recombination machinery. Here, and within the context of Genomic Disorders, we will briefly overview the principal models currently invoked to explain these chromosomal rearrangements, including Non-Allelic Homologous Recombination (NAHR), Fork Stalling Template Switching (FoSTeS), Microhomology Mediated Break-Induced Repair (MMBIR) and Breakage–fusion–bridge cycle (BFB). We will also discuss an unanticipated consequence of certain copy number variations (CNVs) whereby the CNVs potentially compromise fundamental processes controlling genomic stability including DNA replication and the DNA damage response. We will illustrate these using specific examples including Genomic Disorders (DiGeorge/Veleocardiofacial syndrome, HSA21 segmental aneuploidy and rec (3) syndrome) and cell-based model systems. Finally, we will review some of the recent exciting developments surrounding specific CNVs and their contribution to cancer development as well as the latest model for cancer genome rearrangement; ‘chromothripsis’.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history > QH0301 Biology
R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology Including cancer and carcinogens
Depositing User: Philippa Erasmus
Date Deposited: 23 Apr 2012 13:03
Last Modified: 03 Jul 2019 01:47

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