Jan Valka1, Jitka Vesela1, Hana Votavova1, Michaela Dostalova-Merkerova1, Zuzana Horakova1, Vit Campr2, Jana Brezinova1, Zuzana Zemanova3, Anna Jonasova4, Jaroslav Cermak1, Monika Belickova1. 1. Institute of Hematology and Blood Transfusion, Prague, Czech Republic. 2. Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic. 3. Center of Oncocytogenetics, General University Hospital and First Faculty of Medicine of Charles University, Prague, Czech Republic. 4. First Internal Clinic-Clinic of Hematology, General University Hospital, Prague, Czech Republic.
Abstract
BACKGROUND: The high incidence of mutations and cytogenetic abnormalities in patients with myelodysplastic syndrome (MDS) suggests that defects in DNA repair mechanisms. We monitored DNA repair pathways in MDS and their alterations during disease progression. METHODS: Expression profiling of DNA repair genes was performed on CD34+ cells, and paired samples were used for monitoring of RAD51 and XRCC2 gene expression during disease progression. Immunohistochemical staining for RAD51 was done on histology samples. RESULTS: RAD51 and XRCC2 showed differential expression between low-risk and high-risk MDS (P<.0001), whereas RPA3 was generally decreased among the entire cohort (FC=-2.65, P<.0001). We demonstrated that RAD51 and XRCC2 expression gradually decreased during the progression of MDS. Down-regulation of XRCC2 and RAD51 expression was connected with abnormalities on chromosome 7 (P=.0858, P=.0457). Immunohistochemical staining revealed the presence of RAD51 only in the cytoplasm in low-risk MDS, while in both the cytoplasm and nucleus in high-risk MDS. The multivariate analysis identified RAD51 expression level (HR 0.49; P=.01) as significant prognostic factor for overall survival of patients with MDS. CONCLUSIONS: 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.
BACKGROUND: The high incidence of mutations and cytogenetic abnormalities in patients with myelodysplastic syndrome (MDS) suggests that defects in DNA repair mechanisms. We monitored DNA repair pathways in MDS and their alterations during disease progression. METHODS: Expression profiling of DNA repair genes was performed on CD34+ cells, and paired samples were used for monitoring of RAD51 and XRCC2 gene expression during disease progression. Immunohistochemical staining for RAD51 was done on histology samples. RESULTS:RAD51 and XRCC2 showed differential expression between low-risk and high-risk MDS (P<.0001), whereas RPA3 was generally decreased among the entire cohort (FC=-2.65, P<.0001). We demonstrated that RAD51 and XRCC2 expression gradually decreased during the progression of MDS. Down-regulation of XRCC2 and RAD51 expression was connected with abnormalities on chromosome 7 (P=.0858, P=.0457). Immunohistochemical staining revealed the presence of RAD51 only in the cytoplasm in low-risk MDS, while in both the cytoplasm and nucleus in high-risk MDS. The multivariate analysis identified RAD51 expression level (HR 0.49; P=.01) as significant prognostic factor for overall survival of patients with MDS. CONCLUSIONS: 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.
Authors: Michaela Dostalova Merkerova; Jiri Klema; David Kundrat; Katarina Szikszai; Zdenek Krejcik; Andrea Hrustincova; Iva Trsova; Anh Vu LE; Jaroslav Cermak; Anna Jonasova; Monika Belickova Journal: Cancer Genomics Proteomics Date: 2022 Mar-Apr Impact factor: 4.069
Authors: Howard Lopes Ribeiro Junior; Roberta Taiane Germano de Oliveira; Daniela de Paula Borges; Marília Braga Costa; Izabelle Rocha Farias; Antônio Wesley Araújo Dos Santos; Silvia Maria Meira Magalhães; Ronald Feitosa Pinheiro Journal: Med Oncol Date: 2019-10-30 Impact factor: 3.064