Fanconi anemia

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Title: Fanconi anemia
Author: Rosselli, Filippo
Abstract: Fanconi anemia (FA) is a rare human recessive syndrome featuring bone marrow failure, myelodysplasia, and predisposition to cancer as well as chromosome fragility and hypersensitivity to DNA interstrands crosslinking agents. FA was described in 1927 by the Swiss pediatrician Giuseppe Fanconi, which reported a first family with three affected sibling presenting developmental defects and anemia. FA cells are hypersensitive, at both cellular and chromosomal levels, to the exposure to DNA interstrands crosslinking agents, like mitomycin C, diepoxybutane, cis-platinum or photoactivated psoralen. The chromosomal response to DNA interstrands crosslinks (ICLs)-inducing agents is so typical that the observation of both the induced frequency of chromosome aberrations and their type, i.e. tri- and quadri-radials, is considered the best diagnostic criteria for FA. Indeed, looking simply at the clinical hallmarks of the patients, it is difficult to distinguish FA patients from several other bone marrow failure syndromes. Alternatively, since the FA cells need more time to pass through both G2 and S phases than normal cell, the analysis by flow cytometry of the over accumulation of the FA cells in G2 following exposure to ICL-inducing agents could be a useful approach for diagnosis. More recently, molecular and biochemical approaches looking at gene mutations, proteins expression and/or post-translational modifications are used to validate cytogenetics conclusions. To date 19 different genes (FANC) have been associated to FA. The FANC proteins constitute a pathway which essential function is to deal with replication stress assuring the transmission of a stable genome from one cell to the daughters and acting both during replication, to cope with stalled replication forks, but also in G2 and M phases, to resolve un-replicated or not fully replicated regions before telophase. For review: Duxin and Walter, 2015; Bogliolo and Surralles, 2015; Walden and Deans, 2014; Soulier 2011; Lobitz and Velleuer, 2006.
Subject: Fanconi anemia; DNA repair; Replication; Acute Myeloid Leukemia; Bone Marrow Failure; Kprones Section; Animals; DNA/genetics; DNA Damage; *DNA Repair; DNA Replication; Fanconi Anemia/*genetics/metabolism; Humans; Bone Marrow/metabolism/pathology; Chromosome Fragility/genetics; DNA Helicases/*genetics; Fanconi Anemia/*genetics/pathology/*therapy; *Genetic Therapy; Hematopoietic Stem Cell Transplantation; Humans; Mutation; RNA Editing/genetics; Cell Survival
Publisher: ARMGHM - Atlas Génétique des Cancers
Date: 2017

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