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Custom assays for personalized, longitudinal monitoring of circulating tumor DNA using PIPSenSeq

使用 PIPSenSeq 对循环肿瘤 DNA 进行个性化纵向监测的定制检测

基本信息

批准号：
10254378
负责人：
Kristina Fontanez
金额：
$ 82.56万
依托单位：
FLUENT BIOSCIENCES INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-04 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10254378
关键词：
Abate Address Apoptosis Bar Codes Bioinformatics Biological Assay Biological Markers Biological Sciences Blood Boston California Cancer Detection Cancer Patient Cells Clinical Collaborations Complex Computer software Conflict (Psychology)Consensus Consumption Custom DNA DNA sequencing Data Data Analyses Detection Diagnosis Disease Excision Genomics Head and Neck Squamous Cell Carcinoma Individual Informatics Length Libraries Malignant Neoplasms Manuals Methods Microfluidics Minor Modernization Molecular Monitor Mutate Mutation Mutation Detection Necrosis Output Patients Performance Phase Plasma Population Postoperative Period Preparation Protocols documentation Reaction Recurrence Relapse Sampling San Francisco Symptoms Technology Testing Time Tube Tumor Burden Universities amplification detection base cancer biomarkers cancer cell cancer diagnosis cancer recurrence cell free DNA clinical application cost cost effective cost effectiveness design detection assay detection sensitivity digital flexibility follow-up indexing innovation insight instrumentation interest multiplex assay mutant nanoscale neoplastic cell new technology next generation sequencing novel peripheral blood research clinical testing self assembly single molecule tumor tumor DNA

项目摘要

PROJECT SUMMARY / ABSTRACT Targeted DNA sequencing of cell-free tumor DNA (circulating tumor DNA, ctDNA) shed into a patient’s blood holds great promise for detection, diagnosis, and monitoring of cancer. Given that all tumor cells have the potential to shed ctDNA, targeted assays using modern next-generation sequencing methods and digital PCR can provide insight into the entirety of a patient’s tumor burden. ctDNA is therefore an attractive biomarker for diagnosis and monitoring of cancer patients via non-invasive peripheral blood draw. Such assays, however, require ultra-sensitive sequencing fidelity, flexible target multiplexing, and uniform target amplification for efficient, quantitative, and cost-effective testing. In addition, several challenges arise in the implementation of assays to identify and monitor tumor-specific mutations extracted from blood. First, the mutant DNA from cancer cells is rare compared to the background of normal DNA, requiring detection sensitivities below 0.1% for some clinical applications. Second, cell-free DNA extracted from plasma is limited in mass (<100 ng / 5 ml sample), and typically degraded to very short fragment lengths, requiring efficient capture and amplification of the targets of interest. Third, cancer diagnosis and monitoring may require surveillance of a multitude of tumor or patient-specific mutations, requiring multiplex amplification for efficient sample utilization. In collaboration with our academic partners at Boston University and the University of California San Francisco, we have developed a novel next-generation sequencing sample preparation platform that addresses these critical challenges - PIPSenSeq (Pre-templated Instant Partitions for Sensitive Sequencing). This approach takes advantage of molecular indexing for consensus-read sequencing in combination with single-molecule amplification in Poisson-distributed nanoscale partitions. Furthermore, PIPSenSeq provides a simple, rapid library preparation that does not require complex, expensive instrumentation or microfluidic consumables. In this proposal we will develop PIPSenSeq as a commercial-ready platform for cancer monitoring, and demonstrate clinical utility in a study of 60 - 70 head and neck squamous cell carcinoma patients. These patients will be monitored post-operatively for tumor recurrence using personalized PIPSenSeq panels on longitudinally collected ctDNA samples.

项目摘要/摘要