Does interpregnancy BMI change affect the risk of complications in the second pregnancy? : Analysis of pooled data from Aberdeen, Finland and Malta

Open Access via Springer agreementPeer reviewedPublisher PD

A systematic review of circulating predictive and prognostic biomarkers to aid the personalised use of radiotherapy in the radical treatment of patients with oesophageal cancer

Background The availability of circulating biomarkers that are predictive of treatment response or prognostic of overall outcome could enable the personalised and adaptive use of radiotherapy (RT) in patients with oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). Methods A systematic review was carried out following Preferred Reporting Items for Systematic Reviews guidance. Medline, EMBASE, PubMed, Cochrane Library, CINAHL, Scopus and the Web of Science databases were searched for studies published between January 2005-February 2023 relating to circulating biomarkers evaluated in the context of neoadjuvant or definitive RT delivered for OAC/OSCC. Study quality was assessed using predefined criteria. Results A total of 3012 studies were screened and 57 subsequently included, across which 61 biomarkers were reported. A majority (43/57,75.4%) of studies were of Asian origin and retrospective (40/57, 70.2%), with most (52/57, 91.2%) biomarkers reported in the context of patients with OSCC. There was marked inter-study heterogeneity in patient populations, treatment characteristics, biomarker measurement and the cut points used to define biomarker positivity. Nevertheless, there is evidence for the prognostic and predictive value of circulating tumour DNA and numerous miRNAs in OAC and OSCC, as well as for the prognostic and predictive value of circulating levels of CYFRA21.1 in OSCC. Conclusions There is consistent evidence for the potential predictive and prognostic value of a small number of biomarkers in OSCC and OAC, though these data are insufficient for translation to current clinical practice. Well-designed prospective studies are now required to validate their role in stratified and personalised RT treatment approaches

Analysis of the Clinical Advancements for BRCA-Related Malignancies Highlights the Lack of Treatment Evidence for BRCA-Positive Male Breast Cancer

Funding: This research was funded by The University of Aberdeen Development Trust, Breast Cancer UK and NHS Grampian Breast Cancer Endowment Fund. S.C. is in receipt of an Elphinstone Scholarship.Peer reviewedPublisher PD

A suspension technique for efficient large-scale cancer organoid culturing and perturbation screens.

Organoid cell culture methodologies are enabling the generation of cell models from healthy and diseased tissue. Patient-derived cancer organoids that recapitulate the genetic and histopathological diversity of patient tumours are being systematically generated, providing an opportunity to investigate new cancer biology and therapeutic approaches. The use of organoid cultures for many applications, including genetic and chemical perturbation screens, is limited due to the technical demands and cost associated with their handling and propagation. Here we report and benchmark a suspension culture technique for cancer organoids which allows for the expansion of models to tens of millions of cells with increased efficiency in comparison to standard organoid culturing protocols. Using whole-genome DNA and RNA sequencing analyses, as well as medium-throughput drug sensitivity testing and genome-wide CRISPR-Cas9 screening, we demonstrate that cancer organoids grown as a suspension culture are genetically and phenotypically similar to their counterparts grown in standard conditions. This culture technique simplifies organoid cell culture and extends the range of organoid applications, including for routine use in large-scale perturbation screens

Disentangling oncogenic amplicons in esophageal adenocarcinoma

Acknowledgements: The laboratory of R.C.F is supported by a Program Grant from the Medical Research Council (MR/W014122/1). This work was supported by Cancer Research UK (A15874, A22720, A22131). SAZ is supported by a Gates-Cambridge Trust scholarship. We thank the Human Research Tissue Bank, which is supported by the UK National Institute for Health Research (NIHR) Cambridge Biomedical Research Center, from Addenbrooke’s Hospital. This research was supported by the NIHR Cambridge Biomedical Research Center (NIHR203312). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. S.T. and K.N.O. were funded by the MacMillan Family Foundation (60210014) as part of the MacMillan Center for the Study of the Non-Coding Cancer Genome at the New York Genome Center including B.W.’s studentship.Esophageal adenocarcinoma is a prominent example of cancer characterized by frequent amplifications in oncogenes. However, the mechanisms leading to amplicons that involve breakage-fusion-bridge cycles and extrachromosomal DNA are poorly understood. Here, we use 710 esophageal adenocarcinoma cases with matched samples and patient-derived organoids to disentangle complex amplicons and their associated mechanisms. Short-read sequencing identifies ERBB2, MYC, MDM2, and HMGA2 as the most frequent oncogenes amplified in extrachromosomal DNAs. We resolve complex extrachromosomal DNA and breakage-fusion-bridge cycles amplicons by integrating of de-novo assemblies and DNA methylation in nine long-read sequenced cases. Complex amplicons shared between precancerous biopsy and late-stage tumor, an enrichment of putative enhancer elements and mobile element insertions are potential drivers of complex amplicons’ origin. We find that patient-derived organoids recapitulate extrachromosomal DNA observed in the primary tumors and single-cell DNA sequencing capture extrachromosomal DNA-driven clonal dynamics across passages. Prospectively, long-read and single-cell DNA sequencing technologies can lead to better prediction of clonal evolution in esophageal adenocarcinoma