Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Olipitz, W; Hopfinger, G; Aguiar, RC; Gunsilius, E; Girschikofsky, M; Bodner, C; Hiden, K; Linkesch, W; Hoefler, G; Sill, H.
Defective DNA-mismatch repair: a potential mediator of leukemogenic susceptibility in therapy-related myelodysplasia and leukemia.
Genes Chromosomes Cancer. 2002; 34(2):243-248
Doi: 10.1002/gcc.10059
Web of Science
PubMed
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FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Olipitz Werner
- Sill Heinz
- Co-Autor*innen der Med Uni Graz
- Höfler Gerald
- Lind Karin
- Linkesch Werner
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Base Pair Mismatch - genetics
- Child -
- Child, Preschool -
- DNA Repair - genetics
- Female -
- Genetic Predisposition to Disease - genetics
- Humans -
- Infant -
- Leukemia - chemically induced Leukemia - genetics
- Male -
- Middle Aged -
- Myelodysplastic Syndromes - chemically induced Myelodysplastic Syndromes - genetics
- Trinucleotide Repeat Expansion - genetics