Development of diagnostic and prognostic tests for esophageal adenocarcinoma
食管腺癌诊断和预后测试的发展
基本信息
- 批准号:10057357
- 负责人:
- 金额:$ 13.42万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-12-16 至 2022-11-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAllelesBarrett EsophagusBiological AssayBiological MarkersBiopsyCanadaCellsChromosomal RearrangementChronicClinicalCollectionCurative SurgeryCytologyDNADNA copy numberDataDeglutitionDetectionDevelopmentDevicesDiagnosisDiagnostic testsDiseaseDisease ProgressionDysplasiaEarly DiagnosisEncapsulatedEsophageal AdenocarcinomaEsophageal Intraepithelial NeoplasiaEsophagusFDA approvedFoundationsFundingFutureGastroesophageal reflux diseaseGeneticGenetic MarkersGenomicsGoalsGuidelinesIncidenceIndividualInvestigationKnowledgeLarge-Scale SequencingLeadMalignant NeoplasmsMetaplasiaMolecularMutateMutationMutation DetectionNeoadjuvant TherapyOutcomePatient-Focused OutcomesPatientsPlasmaPoriferaPrognosisPrognostic MarkerPublishingRecommendationRecurrenceResourcesRiskSamplingSensitivity and SpecificitySomatic MutationSpecificitySpecimenStagingSurveillance ProgramSurvival RateTestingTimeTissue SampleWorkbasecancer diagnosiscell free DNAchemoradiationchemotherapyclinical biomarkersclinical developmentcomparativedata resourcedetection testeffectiveness evaluationexome sequencinggenetic signaturegenome sequencinggenomic signaturehigh riskimprovedinnovationmultidisciplinarymutantneoplasticnext generation sequencingnovelnovel strategiespatient subsetsprognosticprognostic assaysprognostic valuescreeningsuccesstargeted sequencingtheoriestissue resourcetranscriptome sequencingtumortumor DNAwhole genome
项目摘要
Abstract. The primary goal of this proposal is to develop novel molecular approaches for early detection of
esophageal adenocarcinoma (EAC). EAC arises in the setting of gastroesophageal reflux disease (GERD) and
Barrett's esophagus (BE); a metaplastic change resulting from GERD. This knowledge has driven endoscopic
screening and surveillance recommendations for individuals with GERD and BE but compliance is low and the
vast majority of new EAC cases are still diagnosed at late stage, when the tumor is inoperable and prognosis is
extremely poor. Over the past 6-8 years, we have developed a highly collaborative, multi-institutional and multi-
disciplinary team focused on the development of clinically useful biomarkers for EAC. This proposal will build
on our previously funded projects and the clinical and technical resources available to us through these
studies, in order to evaluate two different approaches to early detection of EAC. The first approach is based on
detection of somatic mutation and DNA copy number abnormality signatures in esophageal cytology samples.
Published studies and our own ongoing work strongly indicate that accumulation of somatic mutations and
major chromosomal rearrangements drive the progression from BE to EAC. We believe that these changes
can be leveraged to identify a genomic signature for progression that can be detected in cytology samples
using a targeted next-generation sequencing (NGS) test. Identification of the genomic signature is ongoing in
our group through large-scale comparative sequencing of EAC and pre-neoplastic tissue samples. To evaluate
the effectiveness of this signature in identifying progression, we are currently collecting ~350 esophageal
cytology samples using an encapsulated sponge called the EsophaCap™. This device is not yet commercially
available, but has been provided to us under arrangement with CapNostics LLC and is currently approved for
investigational testing in the USA and Canada. These unique data and tissue resources will be used in Specific
Aim 1 to evaluate the sensitivity and specificity of a targeted NGS analysis of esophageal cytology samples to
detect dysplasia and early EAC. The second approach also leverages our large-scale sequencing data and
targeted sequencing assays, but in this case we will evaluate the detection of mutations in circulating, cell-free
DNA isolated from plasma as a biomarker for EAC. We are currently collecting plasma from all patients who
swallow the EsophaCap™ device and this provides an excellent tissue resource in which to test detection of
circulating tumor DNA (ctDNA). To aid in the detection of ctDNA, we have developed an ultra-sensitive NGS-
based assay that can detect mutations at multiple loci with sensitivity as low as 0.05% (1/2000) mutant allele
fraction. These resources will be used in Specific Aim 2 in order to evaluate the sensitivity and specificity of
ctDNA for detection of stage I and II EAC. Finally, studies indicate that ctDNA detection may have prognostic
value. In Specific Aim 3 we will evaluate the prognostic value of ctDNA in stage I and II EAC patients with the
hope that this may prove useful for directing neoadjuvant therapy in these patients.
摘要。本提案的主要目标是开发新的分子方法用于早期检测
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Tony E Godfrey其他文献
Tony E Godfrey的其他文献
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{{ truncateString('Tony E Godfrey', 18)}}的其他基金
Development of diagnostic and prognostic tests for esophageal adenocarcinoma
食管腺癌诊断和预后测试的发展
- 批准号:
10308014 - 财政年份:2016
- 资助金额:
$ 13.42万 - 项目类别:
Feasibility of Molecular Cytology for the Management of Barrett's Esophagus
分子细胞学治疗巴雷特食管的可行性
- 批准号:
8880446 - 财政年份:2015
- 资助金额:
$ 13.42万 - 项目类别:
Innovative approach to cancer detection and treatment monitoring
癌症检测和治疗监测的创新方法
- 批准号:
8643777 - 财政年份:2013
- 资助金额:
$ 13.42万 - 项目类别:
Innovative approach to cancer detection and treatment monitoring
癌症检测和治疗监测的创新方法
- 批准号:
8426388 - 财政年份:2013
- 资助金额:
$ 13.42万 - 项目类别:
Impact of Biological, Clinical, and Social Determinants on Trauma and Trauma Outcomes
生物学、临床和社会决定因素对创伤和创伤结果的影响
- 批准号:
10344300 - 财政年份:2010
- 资助金额:
$ 13.42万 - 项目类别:
Impact of Biological, Clinical, and Social Determinants on Trauma and Trauma Outcomes
生物学、临床和社会决定因素对创伤和创伤结果的影响
- 批准号:
10616684 - 财政年份:2010
- 资助金额:
$ 13.42万 - 项目类别:
Biomarkers for Esophageal Cancer Progression and Prognosis
食管癌进展和预后的生物标志物
- 批准号:
7909276 - 财政年份:2009
- 资助金额:
$ 13.42万 - 项目类别:
Biomarkers for Esophageal Cancer Progression and Prognosis
食管癌进展和预后的生物标志物
- 批准号:
7523588 - 财政年份:2008
- 资助金额:
$ 13.42万 - 项目类别:
Biomarkers for Esophageal Cancer Progression and Prognosis
食管癌进展和预后的生物标志物
- 批准号:
7687433 - 财政年份:2008
- 资助金额:
$ 13.42万 - 项目类别:
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