title: Somatic mutations and epigenetic abnormalities in myelodysplastic syndromes.
abstract: During many years, very limited data had been available on specific gene mutations in MDS in particular due to the fact that balanced chromosomal translocations (which have allowed to discover many "leukemia" genes) are very rare in MDS, while chromosomal deletions are generally very large, making it difficult to identify genes of interest. Recently, the advent of next generation sequencing (NGS) techniques has helped identify somatic gene mutations in 75-80% of MDS, that cluster mainly in four functional groups, i.e. cytokine signaling (RAS genes), DNA methylation, (TET2, IDH1/2, DNMT3a genes) histone modifications (ASXL1 and EZH2 genes), and spliceosome (SF3B1 and SRSF2 genes) along with mutations of RUNX1 and TP 53 genes. Most of those mutations, except SF3B1 and TET2 mutations, are associated with an overall poorer prognosis, while some gene mutations (mainly TET2 mutation), may be associated to better response to hypomethylating agents. The frequent mutations of epigenetic modulators in MDS appear to largely contribute to the importance of epigenetic deregulation (in particular gene hypermethylation and histone deacetylation) in MDS progression, and may account at least partially for the efficacy of hypomethylating agents in the treatment of MDS.
authors: Hematology Department, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris (AP-HP), France; Université Paris 7, France; INSERM Unit U944, Hôpital St Louis, Paris, France.
authors: Raphael
authors: R
authors: Itzykson
authors: Laboratoire d'hématologie, Hôpital Cochin, Assistance Publique - Hôpitaux de Paris (AP-HP), France; Université Paris 5, France.
authors: Olivier
authors: O
authors: Kosmider
authors: Hematology Department, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris (AP-HP), France; Université Paris 7, France; INSERM UMR-S-940, Hôpital St Louis, Paris, France. Electronic address: pierre.fenaux@sls.aphp.fr.
authors: Pierre
authors: P
authors: Fenaux
mesh_terms: D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics
keywords: epigenetics; genetics; histone; methylation; myelodysplastic syndromes