PMID- 16104874 OWN - NLM STAT- MEDLINE DCOM- 20050926 LR - 20061115 IS - 0902-4441 (Print) IS - 0902-4441 (Linking) VI - 75 IP - 3 DP - 2005 Sep TI - Absence of p16 and p27 gene rearrangements and mutations in de novo myelodysplastic syndromes. PG - 193-8 AB - 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. FAU - Papageorgiou, Sotirios G AU - Papageorgiou SG AD - Second Department of Internal Medicine Propaedeutic, Athens University Medical School, Attikon General Hospital, Haidari, Greece. sotirispapageorgeiou@hotmail.com FAU - Pappa, Vassiliki AU - Pappa V FAU - Papageorgiou, Efstathios AU - Papageorgiou E FAU - Tsirigotis, Panagiotis AU - Tsirigotis P FAU - Kontsioti, Frida AU - Kontsioti F FAU - Panani, Anna AU - Panani A FAU - Dervenoulas, John AU - Dervenoulas J FAU - Economopoulos, Theofanis AU - Economopoulos T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur J Haematol JT - European journal of haematology JID - 8703985 RN - 0 (Cell Cycle Proteins) RN - 0 (Cyclin-Dependent Kinase Inhibitor p16) RN - 0 (DNA Primers) RN - 0 (Tumor Suppressor Proteins) RN - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27) SB - IM MH - Base Sequence MH - Blotting, Southern MH - Cell Cycle Proteins/*genetics MH - Cyclin-Dependent Kinase Inhibitor p16/*genetics MH - Cyclin-Dependent Kinase Inhibitor p27 MH - DNA Primers MH - Humans MH - Karyotyping MH - *Mutation MH - Myelodysplastic Syndromes/*genetics MH - Polymerase Chain Reaction MH - Polymorphism, Single-Stranded Conformational MH - Tumor Suppressor Proteins/*genetics EDAT- 2005/08/18 09:00 MHDA- 2005/09/27 09:00 CRDT- 2005/08/18 09:00 PHST- 2005/08/18 09:00 [pubmed] PHST- 2005/09/27 09:00 [medline] PHST- 2005/08/18 09:00 [entrez] AID - EJH475 [pii] AID - 10.1111/j.1600-0609.2005.00475.x [doi] PST - ppublish SO - Eur J Haematol. 2005 Sep;75(3):193-8. doi: 10.1111/j.1600-0609.2005.00475.x.