Project description:Rationale: Since January 2014 the Dutch screening programme for bowel cancer has been implemented. Screening will increase the demand for surveillance. Although patients in whom adenomas have been removed are at increased risk of progressing to cancer, solid evidence on the reduction of death from CRC through the current colonoscopy-based surveillance is lacking. Furthermore, colonoscopy-based surveillance leads to high logistic demands, high individual burden and high costs. Therefore, there is need for new surveillance strategies. Stool-based molecular testing (Cologuard, consisting of a stool DNA test and an immunochemical assay for human hemoglobin) or Faecal Immunochemical Testing (FIT) may serve as an alternative for colonoscopy surveillance.
The aim of this study is to compare the accuracy of an established molecular stool test (Cologuard) and FIT to colonoscopy for detection of advanced adenomas or CRC (advanced neoplasia) in a surveillance population. These outcomes will be used to model various strategies of stool-based molecular surveillance to inform health policy decisions.
Project description:Interventions: Collection of whole-stool samples for stool testing primary to surveillance colonoscopy and the completion of a questionnaire.
Primary outcome(s): 1. The accuracy (sensitivity, specificity, PPV and NPV) of the molecular stool test (Cologuard) and FIT compared to colonoscopy in the detection of advanced neoplasia in a surveillance population.
2. Health outcomes and cost-effectiveness of multiple surveillance strategies based on accuracies from endpoint 1.
Study Design: N/A: single arm study, Double blinded (masking used), N/A , unknown, Parallel
Project description:RNA surveillance pathways detect and degrade defective transcripts to ensure RNA fidelity. We find disrupted nuclear RNA surveillance is oncogenic. Cyclin Dependent Kinase 13 (CDK13) is mutated in melanoma and patient-mutated CDK13 accelerates zebrafish melanoma. CDK13 mutation causes aberrant RNA stabilization. CDK13 is required for ZC3H14 phosphorylation, which is necessary and sufficient to promote nuclear RNA degradation. Mutant CDK13 fails to activate nuclear RNA surveillance, causing aberrant protein-coding transcripts to be stabilized and translated. Forced aberrant RNA expression accelerates melanoma in zebrafish. We find recurrent mutations in genes encoding nuclear RNA surveillance components in many malignancies, establishing nuclear RNA surveillance as a tumor-suppressive pathway. Activating nuclear RNA surveillance is crucial to avoid accumulation of aberrant RNAs and their ensuing consequences in development and disease.
Project description:RNA surveillance pathways detect and degrade defective transcripts to ensure RNA fidelity. We find disrupted nuclear RNA surveillance is oncogenic. Cyclin Dependent Kinase 13 (CDK13) is mutated in melanoma and patient-mutated CDK13 accelerates zebrafish melanoma. CDK13 mutation causes aberrant RNA stabilization. CDK13 is required for ZC3H14 phosphorylation, which is necessary and sufficient to promote nuclear RNA degradation. Mutant CDK13 fails to activate nuclear RNA surveillance, causing aberrant protein-coding transcripts to be stabilized and translated. Forced aberrant RNA expression accelerates melanoma in zebrafish. We find recurrent mutations in genes encoding nuclear RNA surveillance components in many malignancies, establishing nuclear RNA surveillance as a tumor-suppressive pathway. Activating nuclear RNA surveillance is crucial to avoid accumulation of aberrant RNAs and their ensuing consequences in development and disease.