title: Haploinsufficiency of RPS14 in 5q- syndrome is associated with deregulation of ribosomal- and translation-related genes.
abstract: We have previously demonstrated haploinsufficiency of the ribosomal gene RPS14, which is required for the maturation of 40S ribosomal subunits and maps to the commonly deleted region, in the 5q- syndrome. Patients with Diamond-Blackfan anaemia (DBA) show haploinsufficiency of the closely related ribosomal protein RPS19, and show a consequent downregulation of multiple ribosomal- and translation-related genes. By analogy with DBA, we have investigated the expression profiles of a large group of ribosomal- and translation-related genes in the CD34(+) cells of 15 myelodysplastic syndrome (MDS) patients with 5q- syndrome, 18 MDS patients with refractory anaemia (RA) and a normal karyotype, and 17 healthy controls. In this three-way comparison, 55 of 579 ribosomal- and translation-related probe sets were found to be significantly differentially expressed, with approximately 90% of these showing lower expression levels in the 5q- syndrome patient group. Using hierarchical clustering, patients with the 5q- syndrome could be separated both from other patients with RA and healthy controls solely on the basis of the deregulated expression of ribosomal- and translation-related genes. Patients with the 5q- syndrome have a defect in the expression of genes involved in ribosome biogenesis and in the control of translation, suggesting that the 5q- syndrome represents a disorder of aberrant ribosome biogenesis.
authors.affiliation: LRF Molecular Haematology Unit, NDCLS, John Radcliffe Hospital, Oxford, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pellagatti
authors.forename: Eva
authors.initials: E
authors.lastname: Hellström-Lindberg
authors.forename: Aristoteles
authors.initials: A
authors.lastname: Giagounidis
authors.forename: Janet
authors.initials: J
authors.lastname: Perry
authors.forename: Luca
authors.initials: L
authors.lastname: Malcovati
authors.forename: Matteo G
authors.initials: MG
authors.lastname: Della Porta
authors.forename: Martin
authors.initials: M
authors.lastname: Jädersten
authors.forename: Sally
authors.initials: S
authors.lastname: Killick
authors.forename: Carrie
authors.initials: C
authors.lastname: Fidler
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: James S
authors.initials: JS
authors.lastname: Wainscoat
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Boultwood
mesh_terms: D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D015536:Down-Regulation; D006238:Haploidy; D006801:Humans; D007621:Karyotyping; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics*
chemical_list: C526722:RPS14 protein, human; D012269:Ribosomal Proteins