Clinical Research Directory

MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies

This is a phase II, open-label, prospective study of T cell receptor alpha/beta depletion (TCR α/β TCD) peripheral blood stem cell (PBSC) transplantation for children and adults with hematological malignancies. This is a safety/feasibility study of the investigational procedure/product.

Linking Somatic Mutation Rate With Baseline Exposure in East Palestine

The goal of this study is to This research team is conducting this study to develop methods to measure the biological impact of exposure to the chemicals released following the February 3, 2023 train derailment on residents of East Palestine, Ohio, and surrounding communities. The main question it aims to answer is: * What biological impact will be measured based on DNA damage? * In participants who provide a biospecimen, how are biomarker changes related to proximity to the derailment and variations in residents' health histories and behaviors? Participants will: * Complete a brief survey asking about experiences related to the February 3, 2023 train derailment, health experiences, and concerns following the derailment, and background information regarding health history. * Possibly contribute biospecimens such as blood, spit, hair, and/or toenail clippings. * Receive communication about study updates and future research opportunities. * A total of 40 study participants will be recruited to participate in a 90-minute interview. The interviews will be video and audio recorded.

Molecular Diagnosis of Systemic Autoinflammatory Diseases

Systemic autoinflammatory diseases (SAIDs) are a set of rare clinically and genetically heterogeneous conditions. The project proposes to identify novel genes and specific signatures in subgroups of patients with SAIDs.

Somatic Mosaicism in Twins Discordant for Childhood Cancer

Somatic mosaicism in cancer associated genes is one potential explanation for discordance in childhood cancer that has not been fully explored to date. This pilot study will focus on twins with central nervous system (CNS) tumors who are identified through the Children's Oncology Group's Project: EveryChild (PEC) registry or volunteer.

UCSF Biobank for Hereditary Cancers and Tumor-Associated Mutations

This is a non-therapeutic clinical research biorepository protocol designed to obtain, store, and clinically annotate biospecimens from participants with hereditary cancers. Those biospecimens will be used to generate participant-derived tumor models that will serve as a resource to better understand hereditary cancers and develop new efficient therapies.

SMS - Study of Somatic Mutations Using Genome Sequencing

Disease and tissue aging are thought to be influenced by genetic changes, or mutations, acquired throughout life. These mutations provide clues regarding the genetic damage that occurred through the lifetime of the patient, and include mutations caused by environmental factors such as ultraviolet light from sunlight or tobacco smoke affecting the skin or internal tissues, respectively. Other mutations may occur due to errors in copying the genome as cells divide. Improvements in technologies that read the genetic code have made it possible for all or selected parts of the genetic code of a human being to be "sequenced", allowing mutations (changes in the genetic code) to be detected.

Development of Polygenic Risk Scores in Colon Cancer Patients Through the Study of Ancestry and Diversity in Genetic Maps of the Brazilian Population - ORIGEM Project

Development of a polygenic risk score based on somatic and germline genetic information from patients with colorectal cancer

SMS 2: Impact of Cancer Therapy on the Somatic Mutational Landscape of Normal Tissues

Recently technology has been developed at the Wellcome Sanger Institute to allow clusters of cells with mutations to be detected in normal and diseased tissues. The researchers wish to determine how the number and nature of these mutant cell clusters change in response to treatments given to cancer patients (such as chemotherapy, radiotherapy, immunotherapy, and drugs targeted at specific mutations in tumours). As such the researchers wish to collect research samples of blood, cheek cells (via swabs) and urine from adult cancer patients receiving the above-mentioned treatments as part of their standard care. The researchers also wish to access any leftover tissue following surgery that is undertaken as part of these patient's treatment.

Somatic Mutation in Chronic Liver Disease

Deaths from chronic liver disease are rising in the UK and around the world. The leading causes are alcohol-related liver disease, metabolic-dysfunction associated steatotic liver disease (MASLD, formerly known as 'non-alcoholic fatty liver disease') and viral hepatitis. Chronic liver disease puts people at significantly increased risk of liver cancer, which in the UK has a 5 year survival of under 15%. Little is understood about how liver cells acquire genetic changes, called somatic mutations, as they progress from healthy cells, to disease, to cancer development. This study aims to investigate these somatic mutations across different causes of chronic liver disease, and different stages of liver disease. The investigators hope this will help us to understand how different insults to the liver put the liver cells under different pressures, resulting in varying genetic changes. By understanding these changes specific to disease aetiology and stage, novel genetic targets may be identified which assist to focus research in identifying specific prognostic, diagnostic and therapeutic tools in chronic liver disease, and improve outcomes for patients. Tissue, surplus to clinical requirement, from patients were undergoing liver biopsy, liver resection or liver transplantation (tissue sampling from explanted liver) collected by collaborators at University of Texas Southwestern will undergo genomic sequencing at the Wellcome Sanger Institute.

Exploring the Landscape of Somatic Mutations in Human Tissue

Every cell in the human body contains a blueprint of the body called the genome. Throughout life, the genome can become damaged resulting in errors (mutations) that can change the way cells behave and may result in diseases such as cancer. Examining the mutations found the genome of both normal (non-cancerous) and diseased cells can give a valuable insight into the very earliest stages of cancer development. Comparing the number and type of mutations in different normal tissues is revealing new insights, helping us to better understand more about why cancer develops.

A Retrospective Study of EGFR-TKIs,Gefitinib, Erlotinib and Osimertinib in NSCLC Patients Treatment

For patients of advanced NSCLC (non small cell lung cancer) , Individualized cancer therapy has been widely accepted since the success of crizotinib administration based on EML4-ALK fusion gene detection and gefitinib and erlotinib administration based on EGFR-TKIs sensitive mutations.From clinical points of view ,individual differences often occur between different patients, leading diverse effect in ADR and drug effect.Meanwhile ,the drug effect and adverse drug reaction was significantly influenced by the pharmacokinetic factors and pharmacodynamic factors.In this research ,we try to establish a more sensitive method to detect sensitive mutations in plasma and discover the correlation between somatic and germline mutations , trough concentration and EGFR-TKI drug effect, the association between ADME-associated SNP ,trough concentration and EGFR-TKI adverse effect .Furthermore, in vivo and in vitro research is also crucial for rational explanation for these clinical phenomenon.

Development of a Predictive Model for the Risk of Metastatic Disease in PPGLs, a Retrospective Cohort Study

Phaeochromocytomas and paragangliomas (PPGLs) are tumours of the adrenal medulla and extra-adrenal sympathetic nervous system, some which can become metastatic. It is a very rare disease and the tumours are often detected late. Approximately 50 % of the tumours are caused by germline genetic variants screening programmes are recommended for patients and their family members; however, they are not yet well-targeted with respect to individual prognosis. In this study the investigatorscaim to characterize the genotype-phenotype associations in all Danish patients (n=400) diagnosed with PPGLs who have been followed in tertiary centres using medical records and national registries. To this end novel immunohistochemical, genetic, and epigenetic biomarkers in tumour tissues samples from biobank material (blood samples and tumour tissue) will be investigated to develop a comprehensive predictive algorithm for disease prognosis. The study will provide a clinical tool for an improved targeted screening program and subsequently prevention of disease development.