Predisposition Footprints in the Somatic Genome of Wilms tumour

Publication: Cancer Discovery

Approximately 10% of children with cancer harbor a mutation in a predisposition gene. In children with the kidney cancer Wilms tumor, the prevalence is as high as 30%. Certain predispositions are associated with defined histological and clinical features, suggesting differences in tumorigenesis. To investigate this, we assembled a cohort of 137 children with Wilms tumor, of whom 71 had a pathogenic germline or mosaic variant. We examined 237 neoplasms (including two secondary leukemias), utilizing whole-genome sequencing, RNA sequencing, and genome-wide methylation, validating our findings in an independent cohort. Tumor development differed in children harboring a predisposition, depending on the variant gene and its developmental timing. Differences pervaded the repertoire of driver events, including high-risk mutations, the clonal architecture of normal kidneys, and the relatedness of neoplasms from the same individual. Our findings indicate that predisposition may preordain Wilms tumorigenesis, suggesting a variant-specific approach to managing children merits consideration. Significance: Tumors that arise in children with a cancer predisposition may develop through the same mutational pathways as sporadic tumors. We examined this question in the childhood kidney cancer, Wilms tumor. We found that certain predispositions dictate the genetic development of tumors, with clinical implications for these children.

View publication

Deconstructing delay discounting in human cocaine addiction using computational modelling and neuroimaging

Publication: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

Michal M Graczyk, Rudolf N Cardinal, Tsen Vei Lim, Salvatore Nigro, Elijah Mak, Karen D Ersche

A preference for sooner-smaller over later-larger rewards, known as delay discounting, is a candidate transdiagnostic marker of waiting impulsivity and a research domain criterion. While abnormal discounting rates have been associated with many psychiatric diagnoses and abnormal brain structure, the underlying neuropsychological processes remain largely unknown. Here, we deconstruct delay discounting into choice and rate processes by testing different computational models and investigate their associations with white matter tracts.

View Publication 

Peripheral innate immunophenotype in neurodegenerative disease: blood-based profiles and links to survival

Publication: Nature

Alexandra Strauss, Peter Swann, Stacey L. Kigar, Rafailia Christou, Natalia Savinykh Yarkoni, Lorinda Turner, Alexander G. Murley, Leonidas Chouliaras, Noah Shapiro, Nicholas J. Ashton, George Savulich, W. Richard Bevan-Jones, Ajenthan Surendranthan, Kaj Blennow, Henrik Zetterberg, John T. O’Brien, James B. Rowe & Maura Malpetti

29 October 2024

Summary

The innate immune system plays an integral role in the progression of many neurodegenerative diseases. In addition to central innate immune cells (e.g., microglia), peripheral innate immune cells (e.g., blood monocytes, natural killer cells, and dendritic cells) may also differ in these conditions. However, the characterization of peripheral innate immune cell types across different neurodegenerative diseases remains incomplete. This study aimed to characterize peripheral innate immune profiles using flow cytometry for immunophenotyping of peripheral blood mononuclear cells.

View publication

Efficacy of Air Cleaning Units for preventing SARS-CoV-2 and other hospital-acquired infections on medicine for older people wards: A quasi-experimental controlled before-and- after study

Publication: Journal of Hospital Infection

Rebecca C. Brock, Robert J.B. Goudie, Christine Peters, Rachel Thaxter, Theodore Gouliouris, Christopher J.R. Illingworth, Andrew Conway Morris, Clive B. Beggs, Matthew Butler, Victoria L. Keevil

5 October 2024

Summary

Researchers have been leading the Addenbrookes Air Disinfection Study (AAirDS) looking at whether Air Cleaning Units in hospital wards reduce hospital-acquired infections, particularly COVID-19.

View publication

Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations 

Publication: Brain

Catarina Rua, Betty Raman, Christopher T Rodgers, Virginia F J Newcombe, Anne Manktelow, Doris A Chatfield, Stephen J Sawcer, Joanne G Outtrim, Victoria C Lupson, Emmanuel A Stamatakis, Guy B Williams, William T Clarke, Lin Qiu, Martyn Ezra, Rory McDonald, Stuart Clare, Mark Cassar, Stefan Neubauer, Karen D Ersche, Edward T Bullmore, David K Menon, Kyle Pattinson, James B Rowe 

08 October 2024

Summary

Damage to the brainstem – the brain’s ‘control centre’ – is behind long-lasting physical and psychiatric effects of severe Covid-19 infection, a study suggests.

Using ultra-high-resolution scanners that can see the living brain in fine detail, researchers from the Universities of Cambridge and Oxford and supported by NIHR Cambridge and Oxford BRCs, were able to observe the damaging effects Covid-19 can have on the brain. Read the full news story.

View publication

How sleep in patients with serious mental illness is recorded and treated, and its impact on service engagement

Aviva Stafford, Sheri Oduola, Sarah Reeve

Published online 10 September 2024


Highlights

  • Sleep is minimally documented in severe mental illness (SMI) patient records.
  • Recommended sleep interventions (e.g., CBT-I) are rarely delivered in SMI settings.
  • Further work is needed to improve sleep assessment and intervention in SMI settings.
  • Targeting sleep in SMI patients could significantly improve symptoms and wellbeing.

View publication

Temporal trends in population attributable fractions of modifiable risk factors for dementia: a time-series study of the English Longitudinal Study of Ageing (2004–2019).

Publication: BMC Medicine

Chen S, Underwood BR, Cardinal RN, Chen X, Chen S, Amin J, Jin H, Mueller C, Yan LL, Brayne C, Kuper H

26 June 2024

Summary

This was an analysis of pre-existing data from the English Longitudinal Study of Ageing, examining changes over time in risk factors for dementia that have the potential to be altered (such as hypertension, obesity, hearing loss, and social isolation).

View publication

Associations between rural/urban status, duration of untreated psychosis and mode of onset of psychosis: a mental health electronic clinical records analysis in the East of England, UK.

Publication: Social Psychiatry and Psychiatric Epidemiology

Kaminska J, Hodgekins J, Lewis JR, Cardinal RN, Oduola S

09 September 2024

Summary

This study examined de-identified NHS data about people having a first episode of psychosis, and looked at how the psychosis began (abruptly or slowly), how long it went untreated, and factors including rural or urban residence. Among such people, some factors differed between rural and urban settings, e.g. employment and living with family. A slow onset of psychosis was associated with a longer time untreated, but rural/urban differences in “time untreated” were not found.

View publication

Cohort study of cardiovascular safety of different COVID-19 vaccination doses among 46 million adults in England

Publication: Nature Communications

Samantha Ip, Teri-Louise North, Fatemeh Torabi, Yangfan Li, Hoda Abbasizanjani, Ashley Akbari, Elsie Horne, Rachel Denholm, Spencer Keene, Spiros Denaxas, Amitava Banerjee, Kamlesh Khunti, Cathie Sudlow, William N. Whiteley, Jonathan A. C. Sterne, Angela M. Wood, Venexia Walker, the CVD-COVID-UK/COVID-IMPACT Consortium & the Longitudinal Health and Wellbeing COVID-19 National Core Study

31 July 2024

Summary

A new study has found heart attacks and strokes were lower after COVID-19 vaccination than before or without vaccination.

View publication

Misexpression of inactive genes in whole blood is associated with nearby rare structural variants

Publication: American Journal of Human Genetics

Thomas Vanderstichele, Katie L. Burnham, Niek de Klein, Michael Inouye, Dirk S. Paul, Emma E. Davenport et al

24 July 2024

Gene misexpression is the aberrant transcription of a gene in a context where it is usually inactive. Despite its known pathological consequences in specific rare diseases, we have a limited understanding of its wider prevalence and mechanisms in humans. To address this, we analyzed gene misexpression in 4,568 whole-blood bulk RNA sequencing samples from INTERVAL study blood donors.

We found that while individual misexpression events occur rarely, in aggregate they were found in almost all samples and a third of inactive protein-coding genes. Using 2,821 paired whole-genome and RNA sequencing samples, we identified that misexpression events are enriched in cis for rare structural variants. We established putative mechanisms through which a subset of SVs lead to gene misexpression, including transcriptional readthrough, transcript fusions, and gene inversion. Overall, we develop misexpression as a type of transcriptomic outlier analysis and extend our understanding of the variety of mechanisms by which genetic variants can influence gene expression.

View publication

© Copyright - NIHR Cambridge Biomedical Research Centre 2025