PMS2 MUTATIONS PROJECT: BIOSPECIMENS PROCUREMENT FOR CHARACTERIZATION FROM HIGH-RISK POPULATION OF CANADIAN INUIT

PMS2 突变项目：采购生物样本以表征加拿大因纽特人高危人群的特征

• 批准号: 10717504
• 负责人: ETHAN DMITROVSKY
• 金额: $ 41.26万
• 依托单位: LEIDOS BIOMEDICAL RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10717504
• 关键词: Blood; Cancer Prevention Trial; Collection; Constitutional; DNA; Data Reporting; Development; Frameshift Mutation; Funding; Generations; Hereditary Nonpolyposis Colorectal Neoplasms; Human; Inuits; Libraries; Malignant Neoplasms; Mismatch Repair Deficiency; Mucous Membrane; Mutation; PMS2 gene; Preventive; RNA; Reagent; Recurrence; Sampling; Syndrome; Testing; Tumor Tissue; Vaccines; Work; base; cancer prevention; cohort; high risk; high risk population; mouse model; mutant mouse model; neoantigen vaccine; next generation sequencing; sample collection; vaccine strategy

DCP hypothesizes that recurrent frame-shift mutations, as observed in Lynch Syndrome, will also occur in Constitutional Mismatch Repair Deficiency (CMMRD) and that the neoantigen vaccine strategy and reagents already under development by DCP will be relevant to cancer prevention in CMMRD Syndrome. To test this hypothesis, DCP is conducting targeted next generation sequencing using a panel of ~30 mononucleotide repeat loci in samples of normal mucosa, tumor tissue, blood (cfDNA and RNA), and fecal DNA from the Pms2 mutant mouse model (GEMM). This will establish the relevance of the mouse model to the available Lynch Syndrome vaccines. If the current vaccines are relevant, they will be tested for cancer preventive efficacy in the GEMM. A biospecimen collection of human samples is needed for the next stage. Specimens from the collection will be sequenced using an expanded panel of ~120 mononucleotide repeat loci. Based on the results, consideration will be given to creation of a new frame-shift vaccine or expanding planned Lynch Syndrome cancer prevention trials to include CMMRD and particularly the high-risk Inuit cohort. The downstream work for generation of sequencing libraries, analysis, and data reporting for human samples obtained for this biospecimen collection will be performed under the DCP-funded severable Unit of Work for the CIPL lab (currently part of NCI Operational Task Order 75N91020F00003).

DCP假设，在Lynch综合征中观察到的复发性帧移突变也会发生在CMMRD中，并且DCP已经开发的新抗原疫苗策略和试剂将与CMMRD综合征的癌症预防有关。