Polycomb-repressive complex 1 (PRC1) and PRC2 maintain repression at many developmental genes in mouse embryonic stem cells and are required for early development. However, it is still unclear how they are targeted and how they function. We show that the ability of RING1B, a core component of PRC1, to ubiquitinate histone H2A is dispensable for early mouse embryonic development and much of the gene repression activity of PRC1. Our data support a model in which PRC1 and PRC2 reinforce each other's binding but suggest that the key functions of PRC1 lie beyond the enzymatic capabilities of RING1B.

Background:Pathological extramural vascular invasion (EMVI) is an independent prognostic factor in rectal cancer, but can also be identified on MRI-detected extramural vascular invasion (mrEMVI). We perform a meta-analysis to determine the risk of metastatic disease at presentation and after surgery in mrEMVI-positive patients compared with negative tumours.Methods:Electronic databases were searched from January 1980 to March 2016. Conventional meta-analytical techniques were used to provide a summative outcome. Quality assessment of the studies was performed.Results:Six articles reported on mrEMVI in 1262 patients. There were 403 patients in the mrEMVI-positive group and 859 patients in the mrEMVI-negative group. The combined prevalence of mrEMVI-positive tumours was 0.346(range=0.198–0.574). Patients with mrEMVI-positive tumours presented more frequently with metastases compared to mrEMVI-negative tumours (fixed effects model: odds ratio (OR)=5.68, 95% confidence interval (CI) (3.75, 8.61), z=8.21, df=2, P<0.001). Patients who were mrEMVI-positive developed metastases more frequently during follow-up (random effects model: OR=3.91, 95% CI (2.61, 5.86), z=6.63, df=5, P<0.001).Conclusions:MRI-detected extramural vascular invasion is prevalent in one-third of patients with rectal cancer. MRI-detected extramural vascular invasion is a poor prognostic factor as evidenced by the five-fold increased rate of synchronous metastases, and almost four-fold ongoing risk of developing metastases in follow-up after surgery.

Adverse features found on rectal MRI identify patients at increased risk of synchronous metastatic disease. This group may benefit from additional preoperative investigation for synchronous metastases such as FDG-PET/CT or liver MRI and from alternative neoadjuvant chemotherapy regimens including induction chemotherapy.

The rate of RNA polymerase II (RNAPII) elongation has an important role in the control of alternative splicing (AS); however, the in vivo consequences of an altered elongation rate are unknown. Here, we generated mouse embryonic stem cells (ESCs) knocked in for a slow elongating form of RNAPII. We show that a reduced transcriptional elongation rate results in early embryonic lethality in mice. Focusing on neuronal differentiation as a model, we observed that slow elongation impairs development of the neural lineage from ESCs, which is accompanied by changes in AS and in gene expression along this pathway. In particular, we found a crucial role for RNAPII elongation rate in transcription and splicing of long neuronal genes involved in synapse signaling. The impact of the kinetic coupling of RNAPII elongation rate with AS is greater in ESC‐differentiated neurons than in pluripotent cells. Our results demonstrate the requirement for an appropriate transcriptional elongation rate to ensure proper gene expression and to regulate AS during development.

Abstract:Aim: To compare the preoperative staging accuracy of CT and 3T MRI in colon cancer, and to investigate the prognostic significance of identified risk factors. Materials and methods: 58 patients undergoing primary resection of their colon cancer were prospectively recruited, with 53 patients included for final analysis. Accuracy of CT and MRI were compared for two readers, using postoperative histology as the gold standard. Patients were followed-up for a median of 39 months. Risk factors were compared by modality and reader in terms of metachronous metastases and DFS, stratified for adjuvant chemotherapy. Results: Accuracy for the identification of T3c+ disease was non-significantly greater on MRI (75% and 79%) than CT (70% and 77%). Differences in the accuracy of MRI and CT for identification of T3+ disease (MRI 75% and 57%, CT 72% and 66%) and N+ disease (MRI 62% and 63%, CT 62% and 56%) were also non-significant. Identification of EMVI+ disease was significantly greater on MRI (75% and 75%) than CT (79% and 54%) for one reader (p=0.029). T3c+ disease on histopathology was the only risk factor which demonstrated a significant difference in rate of metachronous metastases (OR 8.6, p=0.0044) and DFS stratified for adjuvant therapy (OR 4, p=0.048). Conclusion:T3c or greater disease is the strongest risk factor for predicting DFS in colon cancer, Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporationand is accurately identified on imaging. T3c+ disease may therefore be the best imaging entry criteria for trials of neoadjuvant treatment.

Phosphorylation of Ser133 in the transcription factor CREB is an important mechanism for regulating its transcriptional activity, however recent work has suggested significant roles for other regulatory inputs into CREB. To allow study of this in vivo, we have generated a Ser133 to alanine knockin mutation in the mouse CREB locus. As CREB knockout is perinatal lethal, a minigene strategy was used to allow conditional knockin of the Ser133Ala mutation in adult mice using Cre recombinase. While some expression of the mutated protein was observed prior to Cre expression, following Cre expression in either T cells or neurons only the mutated CREB protein was detected.

Objective: The aim of this study was to assess the accuracy of 1.5-T MRI in the pre-operative local T and N staging of colon cancer and identification of extramural vascular invasion (EMVI). Methods: Between 2010 and 2012, 60 patients with adenocarcinoma of the colon were prospectively recruited at 2 centres. 55 patients were included for final analysis. Patients received pre-operative 1.5-T MRI with high-resolution T 2 weighted, gadolinium-enhanced T 1 weighted and diffusion-weighted images. These were blindly assessed by two expert radiologists. Accuracy of the T-stage, N-stage and EMVI assessment was evaluated using post-operative histology as the gold standard. Results: Results are reported for two readers. Identification of T3 disease demonstrated an accuracy of 71% and 51%, sensitivity of 74% and 42% and specificity of 74% and 83%. Identification of N1 disease demonstrated an accuracy of 57% for both readers, sensitivity of 26% and 35% and specificity of 81% and 74%. Identification of EMVI demonstrated an accuracy of 74% and 69%, sensitivity 63% and 26% and specificity 80% and 91%. Conclusion: 1.5-T MRI achieved a moderate accuracy in the local evaluation of colon cancer, but cannot be recommended to replace CT on the basis of this study. Advances in knowledge: This study confirms that MRI is a viable alternative to CT for the local assessment of colon cancer, but this study does not reproduce the very high accuracy reported in the only other study to assess the accuracy of MRI in colon cancer staging.

Imaging plays a vital role informing this decision-making process, both by providing prognostic details about the cancer before the start of treatment and by updating this picture as the cancer responds or fails to respond to treatment. There is a range of available imaging modalities, each with its strengths and weaknesses. Optimizing rectal cancer treatment requires a clear understanding of the important questions that imaging needs to answer and the optimum imaging strategy. Expert Commentary: This article provides an evidence-based review of the available imaging techniques and an expert commentary on the best imaging strategy.