Document Detail


Defective DNA-mismatch repair: a potential mediator of leukemogenic susceptibility in therapy-related myelodysplasia and leukemia.
MedLine Citation:
PMID:  11979558     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the potential role of defective DNA-mismatch repair (MMR) as a mediator of leukemogenic susceptibility in patients with therapy-related myelodysplasia (t-MDS) and leukemia (t-leuk). Thirty-seven individuals with t-MDS/t-leuk were analyzed for microsatellite instability (MSI), the hallmark of defective DNA-MMR. Using standardized international criteria, 5/37 (14%) patients displayed high MSI, whereas 3 other patients had low MSI (8%). To determine the stage at which MSI had developed, we analyzed the primary tumors of 12 patients. Three of 4 patients with high MSI t-MDS/t-leuk also had microsatellite unstable primary tumors. Conversely, MSI was not detected in any primary malignancy of patients with low MSI or microsatellite stable t-MDS/t-leuk (P = 0.0182). In the high MSI group, we further investigated genes targeted by defective DNA-MMR (BAX, TGFBRII, IGFIIR, Caspase-5, APC, PTEN, E2F4, MBD4, MSH6, and MSH3) in both primary tumor and t-MDS/t-leuk. However, no mutation was found in any gene. The significant association of MSI in t-MDS/t-leuk and corresponding primary tumors suggests that defective DNA-MMR confers leukemogenic susceptibility to this cohort of patients.
Authors:
Werner Olipitz; Georg Hopfinger; Ricardo C T Aguiar; Eberhard Gunsilius; Michael Girschikofsky; Claudia Bodner; Karin Hiden; Werner Linkesch; Gerald Hoefler; Heinz Sill
Related Documents :
22657828 - Recruitment of hrdc domain of wrn and blm to the sites of dna damage induced by mytomyc...
24421388 - Dynamic regulation of the cop9 signalosome in response to dna damage.
16836828 - Orientia tsutsugamushi in eschars from scrub typhus patients.
17558848 - A rare transthyretin mutation (asp18glu) associated with vitreous amyloid.
19939458 - Nickel-quinolones interaction. part 2--interaction of nickel(ii) with the antibacterial...
10499838 - Dna encapsulation within co-guanidine membrane coated alginate beads and protection fro...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes, chromosomes & cancer     Volume:  34     ISSN:  1045-2257     ISO Abbreviation:  Genes Chromosomes Cancer     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-05-23     Completed Date:  2002-07-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9007329     Medline TA:  Genes Chromosomes Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  243-8     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Wiley-Liss, Inc.
Affiliation:
Division of Hematology, Department of Medicine, Karl-Franzens University, Graz, Austria.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Base Pair Mismatch* / genetics
Child
Child, Preschool
DNA Repair* / genetics
Female
Genetic Predisposition to Disease / genetics*
Humans
Infant
Leukemia / chemically induced*,  genetics*
Male
Middle Aged
Myelodysplastic Syndromes / chemically induced*,  genetics*
Trinucleotide Repeat Expansion / genetics

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Suppression of the tumorigenic phenotype by chromosome 18 transfer into pancreatic cancer cell lines...
Next Document:  Expression of NUP98/TOP1, but not of TOP1/NUP98, in a treatment-related myelodysplastic syndrome wit...