Development of a low-cost epigenetic screening assay for Pap specimen-based detection of early-stage ovarian cancer in high-risk women
开发一种低成本表观遗传筛查方法,用于基于巴氏标本的高危女性早期卵巢癌检测
基本信息
- 批准号:10317707
- 负责人:
- 金额:$ 44.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-15 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:AchievementAddressBRCA mutationsBenignBioinformaticsBiological AssayBiological MarkersBiometryCancer BiologyCarcinomaCarcinoma in SituCase-Control StudiesCervix UteriClinicalClinical ResearchClinical SensitivityClinical assessmentsComplexCurative SurgeryCytologyDNADNA MethylationDetectionDevelopmentDiagnosisDiscriminationDiseaseDreamsEarly DiagnosisEngineeringEpigenetic ProcessExcisionExhibitsFecesFemale Genital DiseasesFluorescenceGerm-Line MutationGoalsGynecologic PathologyHigh Risk WomanInterceptLaboratoriesLesionLiquid substanceMalignant Epithelial CellMalignant NeoplasmsMalignant neoplasm of ovaryMammalian OviductsMammographyMethodsMethylationMicrofluidic MicrochipsMicrofluidicsMorbidity - disease rateNeoplasm MetastasisOperative Surgical ProceduresOvaryPap smearPathologyPatientsPerformanceRecording of previous eventsResearchResearch PersonnelResolutionSamplingSchemeSensitivity and SpecificitySerousSideSpecificitySpecimenStatistical ModelsSurvival RateSymptomsTechniquesTechnologyTestingTimeTissuesTrainingTranslatingTravelTubeTumor stageUltrasonographyWomanWorkassay developmentbasecancer typecohortcostcost effectivedetection assaydiagnostic technologiesdigitalearly detection biomarkersepigenetic markergenome wide methylationhigh riskimaging modalityimprovedinstrumentationliquid biopsymeltingmethylation biomarkermortalitymultidisciplinarymultiplex assayneoplastic cellnovelperformance testsratiometricscreeningsuccesstumortumor progressionuser-friendlyvariant detection
项目摘要
PROJECT SUMMARY
With a 5-year survival rate of only 47%, high-grade serous carcinoma (HGSC) remains the most lethal of all
types of ovarian cancer. This is a particular concern for women with familial histories or BRCA mutations, who
exhibit 20 to 35-fold higher risk of developing HGSC in their lifetime. The high mortality of the disease is largely
attributable to the fact that HGSC almost always remains undiagnosed until advanced stages when curative
surgery is no longer feasible. Recently, numerous studies have demonstrated that most HGSCs likely originate
in the fallopian tubes as precursor lesions called serous tubal intraepithelial carcinomas (STICs) that progress
over a period of 6-7 years before rapidly metastasizing to the ovary and surrounding tissues. This suggests
there exists a critical window of time in which STIC lesions and early-stage tumors might be detected so that
tumor progression can be effectively intercepted before reaching an incurable stage. Recent studies have held
out hope by showing that STIC and tumor cells are able to freely travel from the fallopian tubes to the cervix
where they can be readily-detected in routinely-collected Pap specimens. Nonetheless, two notable challenges
to this approach remain: (1) issues associated with the sensitivity and specificity of current biomarkers that
undermine test performance and (2) a cost-effective diagnostic technology with sufficient sensitivity to detect
exceedingly-rare copies of biomarkers from early-stage HGSC in complex samples such as Pap specimens.
In the present proposal, we seek to address both of these challenges by developing a new type of HGSC
screening assay called PapDREAM that is based on the sensitive, cost-effective detection of a novel set of
epigenetic biomarkers that we have recently shown to be prevalently and specifically hypermethylated in both
early, precursor (STIC) lesions and later-stage HGSC tumors. The PapDREAM assay will employ a unique,
digital methylation analysis technique called µ-DREAMing (microfluidic Discrimination of Rare EpiAlleles by
Melt) that provides a simple, but highly-effective means of detecting and quantifying rare, aberrantly-
methylated DNA, even in challenging samples such as stool, liquid biopsies and Pap specimens. A user-
friendly workflow based on common laboratory instrumentation will be developed to enable PapDREAM to be
readily translated and performed in various research and clinical settings at a cost of only a few dollars per
assay. Ultimately, the PapDREAM assay can be used alone or in combination with other assays to provide an
ideal screening method for women at high risk for developing HGSC.
We have assembled a multi-disciplinary team with complementary expertise in gynecologic pathology, assay
development and DNA methylation bioinformatics to accomplish this goal by achieving the following aims: (1)
Evaluate and prioritize methylation biomarkers to be included in the PapDREAM assay, (2) Incorporate µ-
DREAMing assays into PapDREAM: a simple, multiplexed digital methylation assay for the detection of early-
stage HGSC, and (3) Assess the clinical performance of the PapDREAM assay in Pap specimens.
项目摘要
5年生存率仅为47%,高级别浆液性癌(HGSC)仍然是所有恶性肿瘤中最致命的
卵巢癌的早期症状对于有家族史或BRCA突变的女性来说,这是一个特别值得关注的问题,
在他们的一生中表现出20至35倍的高风险发展HGSC。这种疾病的高死亡率主要是
这是由于HGSC几乎总是在晚期才被诊断出来,
手术已经不可行了。最近,许多研究表明,大多数HGSCs可能起源于
在输卵管中作为称为浆液性输卵管上皮内癌(STIC)的前驱病变,
在迅速转移到卵巢和周围组织之前,在6-7年的时间内。这表明
存在一个关键的时间窗口,在该时间窗口中可以检测到STIC病变和早期肿瘤,
在达到不可治愈的阶段之前可以有效地阻止肿瘤的发展。最近的研究表明,
通过显示STIC和肿瘤细胞能够自由地从输卵管移动到子宫颈,
在那里它们可以容易地在快速收集的巴氏标本中检测到。然而,两个显著的挑战
这种方法仍然存在:(1)与目前生物标志物的灵敏度和特异性相关的问题,
破坏测试性能和(2)具有足够灵敏度的成本效益诊断技术,以检测
复杂样本(如Pap标本)中早期HGSC生物标志物的罕见拷贝。
在本提案中,我们寻求通过开发一种新型的HGSC来解决这两个挑战
一种名为PapDREAM的筛查方法,该方法基于对一组新的
表观遗传生物标志物,我们最近已经表明,在这两个基因中,
早期前驱(STIC)病变和晚期HGSC肿瘤。PapDREAM测定将采用独特的,
数字甲基化分析技术称为µ-DREAMing(微流控识别稀有表等位基因,
熔融),提供了一种简单,但高度有效的手段,检测和量化罕见的,异常的-
甲基化的DNA,即使在挑战性的样品,如粪便,液体活检和巴氏标本。使用者─
将开发基于通用实验室仪器的友好工作流程,使PapDREAM能够
易于翻译,并在各种研究和临床环境中进行,每个成本仅为几美元。
比色法最终,PapDREAM测定可单独使用或与其他测定组合使用,以提供对细胞的检测。
是一种理想的筛查方法。
我们组建了一支多学科团队,在妇科病理学、检测和诊断方面具有互补的专业知识。
发展和DNA甲基化生物信息学,以实现这一目标,通过实现以下目标:(1)
评价并优先考虑PapDREAM检测中包含的甲基化生物标志物,(2)将μ-
将DREAM检测转化为PapDREAM:一种用于检测早期乳腺癌的简单、多重数字甲基化检测方法。
HGSC期,和(3)评估PapDREAM测定在Pap标本中的临床性能。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Thomas Russell Pisanic II其他文献
Thomas Russell Pisanic II的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Thomas Russell Pisanic II', 18)}}的其他基金
A low-cost, multiplexed digital high resolution melt platform for DNA methylation-based detection and identification of cancers in liquid biopsies
一种低成本、多重数字高分辨率熔解平台,用于液体活检中基于 DNA 甲基化的癌症检测和识别
- 批准号:
10697370 - 财政年份:2022
- 资助金额:
$ 44.38万 - 项目类别:
Development of a low-cost epigenetic screening assay for Pap specimen-based detection of early-stage ovarian cancer in high-risk women
开发一种低成本表观遗传筛查方法,用于基于巴氏标本的高危女性早期卵巢癌检测
- 批准号:
10428656 - 财政年份:2021
- 资助金额:
$ 44.38万 - 项目类别:
Development of a low-cost epigenetic screening assay for Pap specimen-based detection of early-stage ovarian cancer in high-risk women
开发一种低成本表观遗传筛查方法,用于基于巴氏标本的高危女性早期卵巢癌检测
- 批准号:
10678833 - 财政年份:2021
- 资助金额:
$ 44.38万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 44.38万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 44.38万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 44.38万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 44.38万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 44.38万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 44.38万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 44.38万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 44.38万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 44.38万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 44.38万 - 项目类别:
Research Grant














{{item.name}}会员




