314 results match your criteria: "National Institute for Health Research Cambridge Biomedical Research Centre[Affiliation]"
Purpose: ATM germline pathogenic variants (GPVs) are associated with a moderately increased risk of female breast cancer, pancreatic cancer, and prostate cancer. Resources for managing ATM heterozygotes in clinical practice are limited.
Methods: An international workgroup developed a clinical practice resource to guide management of ATM heterozygotes using peer-reviewed publications and expert opinion.
J Natl Cancer Inst
November 2024
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
BJC Rep
April 2024
Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.
J Community Genet
October 2024
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Genet Med
October 2024
Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK.
Purpose: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an extremely rare, highly aggressive cancer (mean age of onset, 24 years). Nearly all cases are associated with somatic or germline pathogenic variants (GPVs) in SMARCA4. Early bilateral oophorectomy is recommended for unaffected females with a SMARCA4 GPV.
View Article and Find Full Text PDFJ Community Genet
October 2024
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Am J Hum Genet
November 2024
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. Electronic address:
Cell Rep
September 2024
Medical Research Council Metabolic Diseases Unit, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK; Department of Obstetrics and Gynaecology and National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK; Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. Electronic address:
Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. Its expression is dysregulated in a number of human diseases, including metabolic disorders and certain cancers. Here, we investigate the developmental regulation and function of Mir483 in vivo.
View Article and Find Full Text PDFEur J Med Genet
December 2024
Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
Background: The South West Thames Centre for Genomics implemented a wider diagnostic Next Generation Sequencing (NGS) gene panel for eligible cancer patients undergoing diagnostic testing whilst restricting data analysis and reporting for BRCA1/BRCA2/PALB2/CHEK2 1100delC only as per contemporaneous guidelines. This study investigated the cost-utility of reanalyzing existing diagnostic grade extended panel data for truncating germline pathogenic variants (GPVs) in known moderate risk cancer susceptibility genes (CSGs) and performing follow-up genetic testing for first-degree relatives if patients have an identified CSG allele.
Methods: Reanalysis of existing NGS data was undertaken in 889 samples from cancer patients contemporaneously eligible through the NHS England National Genomic Test Directory (NGTD) codes R207 (ovarian) or R208 (breast) who had tested negative for BRCA1/BRCA2/PALB2 and CHEK2 1100delC founder variant.
Nat Commun
September 2024
Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Whole genome sequencing (WGS) provides comprehensive, individualised cancer genomic information. However, routine tumour biopsies are formalin-fixed and paraffin-embedded (FFPE), damaging DNA, historically limiting their use in WGS. Here we analyse FFPE cancer WGS datasets from England's 100,000 Genomes Project, comparing 578 FFPE samples with 11,014 fresh frozen (FF) samples across multiple tumour types.
View Article and Find Full Text PDFNat Hum Behav
November 2024
Biostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL.
View Article and Find Full Text PDFDis Model Mech
August 2024
Department of Obstetrics and Gynaecology and National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge CB2 0SW, UK.
The placenta is a gatekeeper between the mother and fetus, adapting its structure and functions to support optimal fetal growth. Studies exploring adaptations of placentae that support the development of genetically small fetuses are lacking. Here, using a mouse model of impaired fetal growth, achieved by deleting insulin-like growth factor 2 (Igf2) in the epiblast, we assessed placental nutrient transfer and umbilical artery (UA) blood flow during late gestation.
View Article and Find Full Text PDFNat Rev Endocrinol
December 2024
Department of Medicine III, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Nat Rev Endocrinol
December 2024
Department of Medicine III, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70-80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. Key differences in the tumour biology and management, together with rare disease incidence and therapeutic challenges in paediatric compared with adult patients, mandate close expert cross-disciplinary teamwork.
View Article and Find Full Text PDFBr J Cancer
September 2024
Genomics England, London, UK.
Background: Sarcomas are diverse neoplasms with highly variable histological appearances in which diagnosis is often challenging and management options for metastatic/unresectable disease limited. Many sarcomas have distinctive molecular alterations, but the range of alterations is large, variable in type and rapidly increasing, meaning that testing by limited panels is unable to capture the broad spectrum of clinically pertinent genomic drivers required. Paired whole genome sequencing (WGS) in contrast allows comprehensive assessment of small variants, copy number and structural variants along with mutational signature analysis and germline testing.
View Article and Find Full Text PDFAnn Oncol
October 2024
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. Electronic address:
Br J Cancer
June 2024
Translational Genetics Team, Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
Background: The CanRisk tool, which operationalises the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) is used by Clinical Geneticists, Genetic Counsellors, Breast Oncologists, Surgeons and Family History Nurses for breast cancer risk assessments both nationally and internationally. There are currently no guidelines with respect to the day-to-day clinical application of CanRisk and differing inputs to the model can result in different recommendations for practice.
Methods: To address this gap, the UK Cancer Genetics Group in collaboration with the Association of Breast Surgery and the CanGene-CanVar programme held a workshop on 16 of May 2023, with the aim of establishing best practice guidelines.
J Med Genet
July 2024
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
Clin Endocrinol (Oxf)
August 2024
Department of Radiology, Section of Nuclear Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Objective: To report our experience with F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with magnetic resonance imaging (MRI) (FET-PET/MRI) in the care trajectory for persistent acromegaly.
Design: Prospective case series.
Patients: Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options.
Am J Hematol
August 2024
Department of clinical genetics/LDGA, Leiden University Medical Centre, Leiden, The Netherlands.
Front Immunol
April 2024
The Comprehensive Transplant Center (CTC) at Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Introduction: We investigated the potential role of HLA molecular mismatches (MM) in achieving stable chimerism, allowing for donor-specific tolerance in patients undergoing combined living donor kidney and hematopoietic stem cell transplantation (HSCT).
Methods: All patients with available DNA samples (N=32) who participated in a phase 2 clinical trial (NCT00498160) where they received an HLA mismatched co-transplantation of living donor kidney and facilitating cell-enriched HSCT were included in this study. High-resolution HLA genotyping data were used to calculate HLA amino acid mismatches (AAMM), Eplet MM, three-dimensional electrostatic mismatch scores (EMS-3D), PIRCHE scores, HLA-DPB1 T-cell epitope group MM, HLA-B leader sequence MM, and KIR ligands MM between the donor and recipient in both directions.
medRxiv
March 2024
Department of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Background: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS).
Methods: We analyzed >22 million variants for 398,238 women.
Eur J Endocrinol
March 2024
Cambridge Endocrine Molecular Imaging Group, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, United Kingdom.
Background: L-[methyl-11C]-methionine-positron emission tomography (Met-PET) is a potentially important imaging adjunct in the diagnostic workup of pituitary adenomas, including somatotroph tumors. Met-PET can identify residual or occult disease and make definitive therapies accessible to a subgroup of patients who would otherwise require lifelong medical therapy. However, existing data on its use are still limited to small case series.
View Article and Find Full Text PDFTrials
February 2024
Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.