例如:"lncRNA", "apoptosis", "WRKY"

Can synthetic lethality approach be used with DNA repair genes for primary and secondary MDS?

Med. Oncol.2019 Oct 30;36(12):99
Howard Lopes Ribeiro Junior 1 , Roberta Taiane Germano de Oliveira 1 , Daniela de Paula Borges 1 , Marília Braga Costa 1 , Izabelle Rocha Farias 1 , Antônio Wesley Araújo Dos Santos 1 , Silvia Maria Meira Magalhães 1 , Ronald Feitosa Pinheiro 2
Howard Lopes Ribeiro Junior 1 , Roberta Taiane Germano de Oliveira 1 , Daniela de Paula Borges 1 , Marília Braga Costa 1 , Izabelle Rocha Farias 1 , Antônio Wesley Araújo Dos Santos 1 , Silvia Maria Meira Magalhães 1 , Ronald Feitosa Pinheiro 2
+ et al

[No authors listed]

Author information
  • 1 Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil.
  • 2 Post-Graduate Program of Pathology, Federal University of Ceara, Fortaleza, Ceara, Brazil. pinheirorfeitosa@gmail.com.

摘要


Cancer-specific defects in DNA repair pathways create the opportunity to employ synthetic lethality approach. Recently, GEMA (gene expression and mutation analysis) approach detected insufficient expression of BRCA or NHEJ (non-homologous end joining) to predict inhibitors response. We evaluated a possible role of DNA repair pathways using gene expression of single-strand break (XPA, XPC, XPG/ERCC5, CSA/ERCC8, and CSB/ERCC6) and double-strand break (ATM, BRCA1, BRCA2, RAD51, XRCC5, XRCC6, LIG4) in 92 patients with myelodysplastic syndrome (73 de novo, 9 therapy-related (t-MDS). Therapy-related MDS (t-MDS) demonstrated a significant downregulation of axis BRCA1-BRCA2-RAD51 comparing to normal controls (p = 0.048, p = 0.001, p = 0.001). XRCC6 showed significantly low expression in de novo MDS comparing to controls (p = 0.039) and for patients who presented chromosomal abnormalities (p = 0.047). Downregulation of LIG4 was consistently associated with poor prognostic markers in de novo MDS (hemoglobin < 8 g/dL (p = 0.040), neutrophils < 800/mm3 (p < 0.001), patients with excess of blasts (p = 0.001), very high (p = 0.002)/high IPSS-R (p = 0.043) and AML transformation (p < 0.001). We also performed an evaluation of GEPIA Database in 30 cancer types and detected a typical pattern of downregulation as here presented in primary or secondary MDS. All these results suggest synthetic lethality approach can be tested with DNA repair genes (beyond that of BRCA1/2 status) for de novo and therapy-related myelodysplastic syndrome and may encourage clinical trials evaluating the use of inhibitors in MDS.

KEYWORDS: DNA repair, Gene expression, Myelodysplastic syndrome, Synthetic lethality