Defective DNA-mismatch repair: A potential mediator of leukemogenic susceptibility in therapy-related myelodysplasia and leukemia

Werner Olipitz, Georg Hopfinger, Ricardo C.T. Aguiar, Eberhard Gunsilius, Michael Girschikofsky, Claudia Bodner, Karin Hiden, Werner Linkesch, Gerald Hoefler, Heinz Sill

Research output: Contribution to journalArticle

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)243-248
Number of pages6
JournalGenes Chromosomes and Cancer
Volume34
Issue number2
DOIs
StatePublished - Jun 11 2002
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Defective DNA-mismatch repair: A potential mediator of leukemogenic susceptibility in therapy-related myelodysplasia and leukemia'. Together they form a unique fingerprint.

Cite this