Augmentation of Myc-Dependent Mitotic Gene Expression by the Pygopus2 Chromatin Effector

Mitotic segregation of chromosomes requires precise coordination of many factors, yet evidence is lacking as to how genes encoding these elements are transcriptionally controlled. Here, we found that the Pygopus (Pygo)2 chromatin effector is indispensable for expression of the MYC-dependent genes that regulate cancer cell division. Depletion of Pygo2 arrested SKOV-3 cells at metaphase, which resulted from the failure of chromosomes to capture spindle microtubules, a critical step for chromosomal biorientation and segregation. This observation was consistent with global chromatin association findings in HeLa S3 cells, revealing the enrichment of Pygo2 and MYC at promoters of biorientation and segmentation genes, at which Pygo2 maintained histone H3K27 acetylation. Immunoprecipitation and proximity ligation assays demonstrated MYC and Pygo2 interacting in nuclei, corroborated in a heterologous MYC-driven prostate cancer model that was distinct from Wnt/β-catenin signaling. Our evidence supports a role for Pygo2 as an essential component of MYC oncogenic activity required for mitosis

Screening for the prevention and early detection of cervical cancer: protocol for systematic reviews to inform Canadian recommendations

Purpose: To inform recommendations by the Canadian Task Force on Preventive Health Care on screening in primary care for the prevention and early detection of cervical cancer by systematically reviewing evidence of (a) effectiveness; (b) test accuracy; (c) individuals’ values and preferences; and (d) strategies aimed at improving screening rates. Methods: De novo reviews will be conducted to evaluate effectiveness and to assess values and preferences. For test accuracy and strategies to improve screening rates, we will integrate studies from existing systematic reviews with search updates to the present. Two Cochrane reviews will provide evidence of adverse pregnancy outcomes from the conservative management of cervical intraepithelial neoplasia. We will search Medline, Embase, and Cochrane Central (except for individuals’ values and preferences, where Medline, Scopus, and EconLit will be searched) via peer-reviewed search strategies and the reference lists of included studies and reviews. We will search ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. Two reviewers will screen potentially eligible studies and agree on those to include. Data will be extracted by one reviewer with verification by another. Two reviewers will independently assess risk of bias and reach consensus. Where possible and suitable, we will pool studies via meta-analysis. We will compare accuracy data per outcome and per comparison using the Rutter and Gatsonis hierarchical summary receiver operating characteristic model and report relative sensitivities and specificities. Findings on values and preferences will be synthesized using a narrative synthesis approach and thematic analysis, depending on study designs. Two reviewers will appraise the certainty of evidence for all outcomes using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and come to consensus. Discussion: The publication of guidance on screening in primary care for the prevention and early detection of cervical cancer by the Task Force in 2013 focused on cytology. Since 2013, new studies using human papillomavirus tests for cervical screening have been published that will improve our understanding of screening in primary care settings. This review will inform updated recommendations based on currently available studies and address key evidence gaps noted in our previous review.Pathology and Laboratory Medicine, Department ofMedicine, Faculty ofReviewedFacult