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

• 批准号: 10650948
• 负责人: Andrew Lin
• 金额: $ 24.82万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10650948
• 关键词: Address; Aggressive behavior; Algorithms; Alkylating Antineoplastic Agents; Anterior Pituitary Gland; Askenazy Cells; Autopsy; Behavior; Benign; Biological Markers; Blindness; Brain; Brain Neoplasms; Characteristics; Chromosomal Loss; Chromosomes; Clinical; Clinical Trials; Clonality; Communities; Consent; Copy Number Polymorphism; DNA methylation profiling; Data; Data Set; Development; Diagnosis; Disease; Disease Progression; Endocrinologist; Epigenetic Process; Excision; Exhibits; Future; Genes; Genetic; Genome; Genomics; Goals; Growth; Incidence; Individual; Indolent; Institution; Intracranial Neoplasms; Invaded; Islet Cell Tumor; Life; Malignant - descriptor; Malignant Epithelial Cell; Malignant Neoplasms; Methylation; Molecular; Morbidity - disease rate; Mutation; National Cancer Institute; Natural History; Neoplasm Metastasis; Neuroendocrine Tumors; Neurologic Dysfunctions; Noise; Operative Surgical Procedures; Oral; Pathway interactions; Patient-Focused Outcomes; Patients; Pattern; Phenotype; Pituitary Corticotropin Secreting Adenoma; Pituitary Gland Adenoma; Pituitary Neoplasms; Pituitary carcinoma; Prevalence; Radiation; Radiation therapy; Recurrence; Registries; Reporting; SEER Program; Sampling; Subgroup; Time; Tumor Bank; United States; Validation; Work; World Health Organization; adenoma; biomarker validation; clinical decision-making; clinical phenotype; clinically relevant; cohort; density; exome sequencing; follow-up; high risk; hormone therapy; improved; lactotroph; men; molecular marker; molecular subtypes; mortality; next generation sequencing; novel therapeutics; predictive marker; prevent; prospective; rapid growth; response; skull base; standard care; standard of care; temozolomide; tumor; tumor registry

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.

项目总结/摘要 一小部分垂体腺瘤表现出攻击性行为，定义为： 治疗，即激素治疗，手术和放射治疗。侵袭性垂体瘤是毁灭性的，生命- 限制性恶性肿瘤具有两种生长模式：（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 缺乏研究和认识不足，部分原因是没有经过验证的生物标志物可以预测未来 攻击性行为我们假设，重复的拷贝数变异模式，包括一个分子 亚二倍体表型，其特征在于染色体1，2，3，6，8，10，11， 图13、15、17、18、21和22中所示的方法预测了放射治疗后的未来进展。另外我们 假设侵袭性垂体腺瘤和癌具有复发性表观遗传和遗传 在基因和途径水平上的改变，定义了更具侵略性的分子亚型。这种基础 需要开展工作，以便临床医生能够前瞻性地识别具有更高恶性潜能的肿瘤。的 鉴定侵袭性疾病的生物标志物对于通过预防侵袭性疾病和非侵袭性疾病来改善患者结果是至关重要的。 过度和治疗不足，以及临床试验开发。