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Background: In this study, the accuracy of preoperative staging for gastric stump cancer, which has not been thoroughly investigated since the condition is rare, was investigated using computed tomography and gastroscopic imaging., Methods: Between February 1994 and April 2018, 49 patients with gastric stump cancer, following subtotal or total gastrectomy, were reviewed retrospectively. Preoperative diagnoses of clinical T and clinical N categories were compared with post-operative pathological diagnoses (pT and pN categories). Positive predictive values, accuracy, sensitivity and specificity were also evaluated., Results: The overall accuracy of T staging was 40.8%. The positive predictive value for cT3/T4 was 96.3%, whereas the positive predictive value for cT1/T2 was 72.7%. The overall accuracy for N staging was 61.2%. The positive predictive value of lymph node positive patients was 73.3%. The positive predictive value and sensitivity of over stage II were 96.6% and 84.8%, respectively., Conclusions: The accuracy of preoperative diagnosis using both computed tomography and gastroscopy imaging may be feasible for T3/T4 advanced gastric stump cancer, whereas diagnosing T1/2 gastric stump cancer must be carefully considered due to high misdiagnosis rates, relating to depth., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Mcm2-7 is recruited to eukaryotic origins of DNA replication by origin recognition complex, Cdc6 and Cdt1 thereby licensing the origins. Cdc6 is essential for origin licensing during DNA replication and is readily destabilized from chromatin after Mcm2-7 loading. Here, we show that after origin licensing, deregulation of Cdc6 suppresses DNA replication in Xenopus egg extracts without the involvement of ATM/ATR-dependent checkpoint pathways. DNA replication is arrested specifically after chromatin binding of Cdc7, but before Cdk2-dependent pathways and deregulating Cdc6 after this step does not impair activation of origin firing or elongation. Detailed analyses revealed that Cdc6 deregulation leads to strong suppression of Cdc7-mediated hyperphosphorylation of Mcm4 and subsequent chromatin loading of Cdc45, Sld5 and DNA polymerase α. Mcm2 phosphorylation is also repressed although to a lesser extent. Remarkably, Cdc6 itself does not directly inhibit Cdc7 kinase activity towards Mcm2-4-6-7 in purified systems, rather modulates Mcm2-7 phosphorylation on chromatin context. Taken together, we propose that Cdc6 on chromatin acts as a modulator of Cdc7-mediated phosphorylation of Mcm2-7, and thus destabilization of Cdc6 from chromatin after licensing is a key event ensuring proper transition to the initiation of DNA replication.