title: Absence of p16 and p27 gene rearrangements and mutations in de novo myelodysplastic syndromes.
abstract: Myelodysplastic syndromes (MDS) represent a group of clonal hematopoietic disorders characterized by dyshemopoiesis and frequent evolution to acute leukemia. Tumor suppressor gene inactivation may be involved in MDS pathogenesis. The two families of cyclin-dependent kinase inhibitors (CDKIs) (INK4 family of p15, p16, p18 and p19 and CIP/KIP family of p21, p27 and p57) that negatively regulate cell cycle progression are known tumor suppressor genes. To determine whether genetic alterations of p16 and p27 genes play an important role in MDS pathogenesis, we examined DNA from 51 patients classified as 17 refractory anemias (RA), four refractory anemias with ringed sideroblasts (RARS), 19 refractory anemias with an excess of blasts (RAEB), 5 refractory anemias with excess of blasts in transformation (RAEB-t) and 6 chronic myelomonocytic leukemias (CMML). Southern blot analysis detected no homozygous deletions of p16 and p27. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing did not reveal point mutations for both genes with the exception of two allelic polymorphisms, namely a C --> G transition at 447 bp of p16exon3 and a T --> A transition at 791 bp of p27exon1 genes. Our results suggest that mutations of p16 and p27 genes resulting in abnormal p16 and p27 proteins do not represent a mechanism of gene inactivation involved in the pathogenesis of MDS.
authors.affiliation: Second Department of Internal Medicine Propaedeutic, Athens University Medical School, Attikon General Hospital, Haidari, Greece. sotirispapageorgeiou@hotmail.com
authors.forename: Sotirios G
authors.initials: SG
authors.lastname: Papageorgiou
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Pappa
authors.forename: Efstathios
authors.initials: E
authors.lastname: Papageorgiou
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tsirigotis
authors.forename: Frida
authors.initials: F
authors.lastname: Kontsioti
authors.forename: Anna
authors.initials: A
authors.lastname: Panani
authors.forename: John
authors.initials: J
authors.lastname: Dervenoulas
authors.forename: Theofanis
authors.initials: T
authors.lastname: Economopoulos
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D018797:Cell Cycle Proteins / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017931:DNA Primers; D006801:Humans; D007621:Karyotyping; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27