Differential expression of homologous recombination DNA repair genes in the early and advanced stages of myelodysplastic syndrome

Abstract

Our study demonstrates that the expression of DNA repair factors, primarily RAD51 and XRCC2, is deregulated in patients with MDS and presents a specific pattern with respect to prognostic categories.

Genetic Variant Screening of DNA Repair Genes in Myelodysplastic Syndrome Identifies a Novel Mutation in the <b><i>XRCC2</i></b> Gene

“…The XRCC2 gene expression level in this patient was significantly decreased by more than 4-fold and was comparable to other patients with monosomy 7 or complex karyotype. As described in our previous study, the XRCC2 gene showed significantly lower levels of expression in the group of MDS patients with chromosome 7 abnormalities than in the rest of the MDS patients [21]. Decreased expression levels were also present for all genes functionally connected with mutated XRCC2 : ATM , BRCA1 , BRCA2 , MRE11A , RAD51 , RAD51B , RAD51C , RAD51D , and RAD52 .…”

“…The number of various genetic and cytogenetic alterations described in the last few years [5-7, 9] and our recent results showing deregulated DNA repair gene expression in MDS cases [21] support the theory that MDS is a disease of genomic instability [10]. Though mutations in the TP53 gene and their relationship with MDS are already known, no mutations in genes directly involved in DNA repair have been described.…”

“…Moreover, the expression of these mutated genes was evaluated using expression data from a previous study performed on the same patient cohort [21]. A heterozygous frameshift mutation caused by the deletion of 2 base pairs in codon 263 of the XRCC2 gene ( XRCC2 : c.789_790delCA) was detected in 1 patient diagnosed with MDS RAEB-2.…”

“…All patient samples were collected at the time of diagnosis. The same cohort of 16 patients with MDS and 4 age-matched controls was used for gene expression analysis in a previous study [21]. …”

Introductory Chapter: Progress in Myelodysplastic Syndrome Area

“…Aberrations in DNA damage response/repair genes other than TP53 and some genes involved in DNA damage checkpoints are rare. Differential expression of homologous recombination DNA repair-associated genes during MDS progression was detected and could be confirmed as new biomarkers related to pathogenesis and poor prognosis in MDS [17,18].…”