For this study we used a potent selective PARP1-inhibitor Bortezomib 179324-69-7 BMN673, that has shown very encouraging results in phase I/II trials. Here we show that MRN is frequently lost in EC, which leads to increased PARP inhibitor sensitivity. This may be exploited for treatment of patients with EC harbouring loss of the MRNcomplex. The goal of this study is to show the frequency of loss of MRE11 and MRN-complex in EC and whether this leads to increased sensitivity to PARP-inhibitors exploiting MRE11 as a potential synthetic lethal gene. This is the first report to show that not only the protein expression of MRE11 but also the expression of the other members of the MRN-complex, RAD50 and NBS1, are lost in a substantial proportion of the ECs. Furthermore, we observed a significant association between protein loss of all MRN members as well as mismatch repair protein status in this large dataset. Protein expression of the MRN-complex has not yet been studied in EC tumours. In bladder cancer, MRE11 has been shown to exhibit predictive properties for radiotherapy treatment. Furthermore, complete loss of MRN-complex in MSI positive colorectal cancers is a frequent event, whereas loss of MRE11 in breast tumours is found only in 9% of cases. Although a clear correlation between mutational status and loss of protein expression could not be found in this study, it is remarkable that a high correlation of protein loss of all MRN members as well as MSI status was found in this large dataset. Confounding results on the mutational status of the MRE11 polyT allele may be related to known difficulties in sequencing of the MRE11 polyT allele due to mispairing of the polymerase enzyme. A previous study revealed high frequency of alterations of DSB repair genes in MSI positive ECs, where MRE11 and RAD50 exhibited heterozygous and homozygous mutations in 51% and 17%, respectively, without examining the impact of the loss of the proteins. Mutations of the MRE11 polyT allele are predominantly heterozygous mutations and it has been suggested that only those with mutations of two and more nucleotides as well as homozygous mutations have a functional impact in terms of loss of function. In this report, we cannot confirm the high frequency of intronic mutations but provide evidence that MRE11 protein is lost in a substantial proportion of ECs. Recently, it has been shown that whole exon sequencing of MRE11 revealed mutations in 1.9% of the EC tumours within the exons. However, intronic mutations have not been assessed, explaining why the frequency of MRE11 mutations is reported to be low not only in the study by Price et al. but also in a recent one by The Cancer Genome Atlas Research Network. PARP inhibitors have shown remarkable sensitivity in BRCA1/ 2-deficient tumour models in vitro as well as in clinical trials involving ALK5 Inhibitor II carriers of BRCA1/2 germ line mutations. Further evolving evidence, however, suggests the potential for a broader scope for PARP inhibitor activity. In fact, for EC we have previously proposed loss of PTEN expression as a potential biomarker for the treatment with PARP-inhibitors based on preclinical data as well as on a clinical case report. Other studies however, have been questioning the role of PTEN in HR, suggesting that this might be a cell line specific phenomenon. Nevertheless, the exact mechanism of the involvement of PTEN in HR DNA repair remains to be elucidated. Loss of MRE11 expression has been suggested to sensitize colorectal, breast and haematological cancer cell lines to PARP-inhibitors due to impaired HR DNA repair. Our report suggests, for the first time, the potential use of PARP inhibitors in the treatment of endometrial cancer based on preclinical findings.