The relationship between the gastric cancer microbiome and clinicopathological factors: a metagenomic investigation from the 100,000 genomes project and The Cancer Genome Atlas.

Background: Findings from previous gastric cancer microbiome studies have been conflicting, potentially due to patient and/or tumor heterogeneity. The intratumoral gastric cancer microbiome and its relationship with clinicopathological variables have not yet been characterized in detail. We hypothesized that variation in gastric cancer microbial abundance, alpha diversity, and composition is related to clinicopathological characteristics.

Proteome-wide forced interactions reveal a functional map of cell-cycle phospho-regulation in .

Dynamic protein phosphorylation and dephosphorylation play an essential role in cell cycle progression. Kinases and phosphatases are generally highly conserved across eukaryotes, underlining their importance for post-translational regulation of substrate proteins. In recent years, advances in phospho-proteomics have shed light on protein phosphorylation dynamics throughout the cell cycle, and ongoing progress in bioinformatics has significantly improved annotation of specific phosphorylation events to a given kinase.

The ATOM-Seq sequence capture panel can accurately predict microsatellite instability status in formalin-fixed tumour samples, alongside routine gene mutation testing.

Microsatellite instability (MSI) occurs across a number of cancers and is associated with different clinical characteristics when compared to microsatellite stable (MSS) cancers. As MSI cancers have different characteristics, routine MSI testing is now recommended for a number of cancer types including colorectal cancer (CRC). Using gene panels for sequencing of known cancer mutations is routinely performed to guide treatment decisions.

The genomic landscape of 2,023 colorectal cancers.

Colorectal carcinoma (CRC) is a common cause of mortality, but a comprehensive description of its genomic landscape is lacking. Here we perform whole-genome sequencing of 2,023 CRC samples from participants in the UK 100,000 Genomes Project, thereby providing a highly detailed somatic mutational landscape of this cancer. Integrated analyses identify more than 250 putative CRC driver genes, many not previously implicated in CRC or other cancers, including several recurrent changes outside the coding genome.

Improved detection of colibactin-induced mutations by genotoxic E. coli in organoids and colorectal cancer.

Co-culture of intestinal organoids with a colibactin-producing pksE. coli strain (EcC) revealed mutational signatures also found in colorectal cancer (CRC). E.

Associations between AI-Assisted Tumor Amphiregulin and Epiregulin IHC and Outcomes from Anti-EGFR Therapy in the Routine Management of Metastatic Colorectal Cancer.

Purpose: High tumor production of the EGFR ligands, amphiregulin (AREG) and epiregulin (EREG), predicted benefit from anti-EGFR therapy for metastatic colorectal cancer (mCRC) in a retrospective analysis of clinical trial data. Here, AREG/EREG IHC was analyzed in a cohort of patients who received anti-EGFR therapy as part of routine care, including key clinical contexts not investigated in the previous analysis.

Experimental Design: Patients who received panitumumab or cetuximab ± chemotherapy for treatment of RAS wild-type mCRC at eight UK cancer centers were eligible.

Loss of TET2 in human hematopoietic stem cells alters the development and function of neutrophils.

Somatic mutations commonly occur in hematopoietic stem cells (HSCs). Some mutant clones outgrow through clonal hematopoiesis (CH) and produce mutated immune progenies shaping host immunity. Individuals with CH are asymptomatic but have an increased risk of developing leukemia, cardiovascular and pulmonary inflammatory diseases, and severe infections.

The risk of colorectal cancer in individuals with mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene: An English population-based study.

Background: Studies have demonstrated a higher risk of developing colorectal cancer (CRC) in individuals with Cystic Fibrosis (CF), and also a potentially increased risk in carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations. Life expectancy for those with CF is rising, increasing the number at risk of developing CRC.

Methods: The incidence of CRC amongst individuals with CF was calculated using data from CORECT-R and linked UK CF Registry and Secondary User Services (SUS) data.

An Enzyme with High Catalytic Proficiency Utilizes Distal Site Substrate Binding Energy to Stabilize the Closed State but at the Expense of Substrate Inhibition.

Understanding the factors that underpin the enormous catalytic proficiencies of enzymes is fundamental to catalysis and enzyme design. Enzymes are, in part, able to achieve high catalytic proficiencies by utilizing the binding energy derived from nonreacting portions of the substrate. In particular, enzymes with substrates containing a nonreacting phosphodianion group coordinated in a distal site have been suggested to exploit this binding energy primarily to facilitate a conformational change from an open inactive form to a closed active form, rather than to either induce ground state destabilization or stabilize the transition state.

Sparse modelling of cancer patients' survival based on genomic copy number alterations.

Copy number alterations (CNA) are structural variation in the genome, in which some regions exhibit more or less than the normal two chromosomal copies. This genomic CNA profile provides critical information in tumour progression and is therefore informative for patients' survival. It is currently a statistical challenge to model patients' survival using their genomic CNA profiles while at the same time identify regions in the genome that are associated with patients' survival.

Forced association of SARS-CoV-2 proteins with the yeast proteome perturb vesicle trafficking.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly infectious coronavirus disease COVID-19. Extensive research has been performed in recent months to better understand how SARS-CoV-2 infects and manipulates its host to identify potential drug targets and support patient recovery from COVID-19. However, the function of many SARS-CoV-2 proteins remains uncharacterised.

Correction: Developing a Raman spectroscopy-based tool to stratify patient response to pre-operative radiotherapy in rectal cancer.

Correction for 'Developing a Raman spectroscopy-based tool to stratify patient response to pre-operative radiotherapy in rectal cancer' by Chloe J. Kirkby et al., Analyst, 2021, 146, 581-589, DOI: .

Luminal Bioavailability of Orally Administered ω-3 PUFAs in the Distal Small Intestine, and Associated Changes to the Ileal Microbiome, in Humans with a Temporary Ileostomy.

Background: Oral administration of purified omega-3 (ω-3) PUFAs is associated with changes to the fecal microbiome. However, it is not known whether this effect is associated with increased PUFA concentrations in the gut.

Objectives: We investigated the luminal bioavailability of oral ω-3 PUFAs (daily dose 1 g EPA and 1g DHA free fatty acid equivalents as triglycerides in soft-gel capsules, twice daily) and changes to the gut microbiome, in the ileum.

Characterisation of dysplastic liver nodules using low-pass DNA sequencing and detection of chromosome arm-level abnormalities in blood-derived cell-free DNA.

High-grade dysplasia carries significant risk of transformation to hepatocellular carcinoma (HCC). Despite this, at the current standard of care, all non-malignant hepatic nodules including high-grade dysplastic nodules are managed similarly. This is partly related to difficulties in distinguishing high-risk pathology in the liver.

EGFR Amplification in Metastatic Colorectal Cancer.

Background: EGFR amplification occurs in about 1% of metastatic colorectal cancers (mCRCs) but is not routinely tested as a prognostic or predictive biomarker for patients treated with anti-EGFR monoclonal antibodies. Herein, we aimed to characterize the clinical and molecular landscape of EGFR-amplified mCRC.

Methods: In this multinational cohort study, we compared clinical data of 62 patients with EGFR-amplified vs 1459 EGFR nonamplified mCRC, as well as comprehensive genomic data of 35 EGFR-amplified vs 439 EGFR nonamplified RAS/BRAF wild-type and microsatellite stable (MSS) tumor samples.

Ectopic humanized mesenchymal niche in mice enables robust engraftment of myelodysplastic stem cells.

Myelodysplastic syndrome (MDS) are clonal stem cell diseases characterized mainly by ineffective hematopoiesis. Here, we present an approach that enables robust long-term engraftment of primary MDS stem cells (MDS-SCs) in mice by implantation of human mesenchymal cell-seeded scaffolds. Critically for modelling MDS, where patient sample material is limiting, mononuclear bone marrow cells containing as few as 10 CD34 cells can be engrafted and expanded by this approach with the maintenance of the genetic make-up seen in the patients.

An open-source, expert-designed decision tree application to support accurate diagnosis of myeloid malignancies.

Accurate, reproducible diagnoses can be difficult to make in haemato-oncology due to multi-parameter clinical data, complex diagnostic criteria and time-pressured environments. We have designed a decision tree application (DTA) that reflects WHO diagnostic criteria to support accurate diagnoses of myeloid malignancies. The DTA returned the correct diagnoses in 94% of clinical cases tested.

Microbiome Analysis of More Than 2,000 NHS Bowel Cancer Screening Programme Samples Shows the Potential to Improve Screening Accuracy.

Purpose: There is potential for fecal microbiome profiling to improve colorectal cancer screening. This has been demonstrated by research studies, but it has not been quantified at scale using samples collected and processed routinely by a national screening program.

Experimental Design: Between 2016 and 2019, the largest of the NHS Bowel Cancer Screening Programme hubs prospectively collected processed guaiac fecal occult blood test (gFOBT) samples with subsequent colonoscopy outcomes: blood-negative [ = 491 (22%)]; colorectal cancer [ = 430 (19%)]; adenoma [ = 665 (30%)]; colonoscopy-normal [ = 300 (13%)]; nonneoplastic [ = 366 (16%)].