Detection of mutator phenotype in Brazilian patients with acute and chronic myeloid leukemia

Abstract

The multisteps of tumorigenesis involve the classic chromosomal instability and the mutator phenotype pathways featured by a predisposition to acquire mutations in tumor suppressor genes and oncogenes. Expansion and contraction of microsatellite sequences due to a deficient mismatch repair system are a marker of the mutator phenotype. Controversial results regarding the extent of microsatellite instability (MSI) have been reported in the development and progression of myeloid malignancies. Here, we investigated MSI and loss of heterozygosity (LOH) frequencies at the microsatellite loci BAT-26, D7S486, D8S135, ANK1, IFNA, TP53 and bcr of 19 Brazilian patients with acute (AML) and chronic myeloid leukemia (CML). One AML patient and one CML patient were categorized as having a high degree of microsatellite instability (MSI-H), corresponding to 10.5% (2/19) of all patients. LOH at loci BAT-26 and TP53 was present in 30% of the patients with AML alone. Despite the small sample size, our results suggest that the mutator phenotype, as verified by MSI frequency, could play a role in the leukemogenesis of a small subset of patients with myeloid leukemia.

Low doses of gamma ionizing radiation increase hprt mutant frequencies of TK6 cells without triggering the mutator phenotype pathway

“…110.96, 296.33, and 31.96 for the mutant frequencies of the groups exposed to 0.2, 0.5, and 1.0 Gy, respectively. p = 0.001. microsatellite instability frequency higher than 30%, using a panel of microsatellite markers (Ayres et al, 2004). Moreover, hprt mutant selection is a rare event measured per~10 -6 assayed cells, in which it is assumed that only one mutant clone gives raise to each positive colony (Albertini et al, 2000).…”