Molecular biomarkers of future aggressive behavior in pituitary tumors
垂体瘤未来攻击行为的分子生物标志物
基本信息
- 批准号:10650948
- 负责人:
- 金额:$ 24.82万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-15 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAggressive behaviorAlgorithmsAlkylating Antineoplastic AgentsAnterior Pituitary GlandAskenazy CellsAutopsyBehaviorBenignBiological MarkersBlindnessBrainBrain NeoplasmsCharacteristicsChromosomal LossChromosomesClinicalClinical TrialsClonalityCommunitiesConsentCopy Number PolymorphismDNA methylation profilingDataData SetDevelopmentDiagnosisDiseaseDisease ProgressionEndocrinologistEpigenetic ProcessExcisionExhibitsFutureGenesGeneticGenomeGenomicsGoalsGrowthIncidenceIndividualIndolentInstitutionIntracranial NeoplasmsInvadedIslet Cell TumorLifeMalignant - descriptorMalignant Epithelial CellMalignant NeoplasmsMethylationMolecularMorbidity - disease rateMutationNational Cancer InstituteNatural HistoryNeoplasm MetastasisNeuroendocrine TumorsNeurologic DysfunctionsNoiseOperative Surgical ProceduresOralPathway interactionsPatient-Focused OutcomesPatientsPatternPhenotypePituitary Corticotropin Secreting AdenomaPituitary Gland AdenomaPituitary NeoplasmsPituitary carcinomaPrevalenceRadiationRadiation therapyRecurrenceRegistriesReportingSEER ProgramSamplingSubgroupTimeTumor BankUnited StatesValidationWorkWorld Health Organizationadenomabiomarker validationclinical decision-makingclinical phenotypeclinically relevantcohortdensityexome sequencingfollow-uphigh riskhormone therapyimprovedlactotrophmenmolecular markermolecular subtypesmortalitynext generation sequencingnovel therapeuticspredictive markerpreventprospectiverapid growthresponseskull basestandard carestandard of caretemozolomidetumortumor registry
项目摘要
Project Summary/Abstract
A small subset of pituitary adenomas demonstrates aggressive behavior as defined by rapid growth following
treatment, namely hormonal therapy, surgery, and radiation. Aggressive pituitary tumors are devastating, life-
limiting malignancies with two patterns of growth: (1) they can remain confined to the skull base and grow
relentlessly, resulting in progressive neurologic dysfunction or (2) they can metastasize. These tumors are
poorly studied and under-recognized in part because there are no validated biomarkers that predict future
aggressive behavior. We hypothesize that recurrent patterns of copy number variation, including a molecular
hypodiploidy phenotype, characterized by an early, clonal loss of one copy of chromosomes 1, 2, 3, 6, 8, 10, 11,
13, 15, 17, 18, 21, and 22, predict future progression following treatment with radiotherapy. Additionally, we
hypothesize that aggressive pituitary adenomas and carcinomas harbor recurrent epigenetic and genetic
alterations at a gene and pathway level that define a more aggressive molecular subtype. This foundational
work is needed so that clinicians can prospectively identify tumors with a higher malignant potential. The
identification of a biomarker of aggressive disease is critical for improving patient outcomes by preventing both
over- and undertreatment, and for clinical trial development.
项目概要/摘要
一小部分垂体腺瘤表现出攻击性行为,定义为以下快速生长
治疗,即激素治疗、手术和放射治疗。侵袭性垂体瘤具有毁灭性、致命性
通过两种生长模式限制恶性肿瘤:(1)它们可以保持局限于颅底并生长
无情地,导致进行性神经功能障碍或(2)它们可以转移。这些肿瘤是
研究不足且认识不足,部分原因是没有经过验证的生物标志物可以预测未来
攻击行为。我们假设拷贝数变异的重复模式,包括分子
亚二倍体表型,其特征是 1、2、3、6、8、10、11 号染色体的一个副本的早期克隆丢失,
13、15、17、18、21 和 22 预测放射治疗后的未来进展。此外,我们
假设侵袭性垂体腺瘤和癌具有复发性表观遗传和遗传性
基因和通路水平的改变定义了更具攻击性的分子亚型。这个基础的
需要开展工作,以便临床医生能够前瞻性地识别具有较高恶性潜力的肿瘤。这
鉴定侵袭性疾病的生物标志物对于通过预防这两种疾病来改善患者的治疗结果至关重要
过度治疗和治疗不足,以及临床试验开发。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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