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.

项目摘要/摘要 一小部分垂体腺瘤表现出了侵略性行为，如在 治疗，即荷尔蒙治疗，手术和辐射。侵略性垂体肿瘤是毁灭性的，生命 - 以两种增长模式限制恶性肿瘤：（1）它们可以局限于颅底并成长 不懈地，导致进行性神经系统功能障碍或（2）它们可以转移。这些肿瘤是 研究不足，部分原因不足，部分原因是没有经过验证的生物标志物可以预测未来 侵略性行为。我们假设拷贝数变化的复发模式，包括分子 下型表型，其特征在于染色体1、2、3、6、8、10、11的一个早期的克隆损失 13、15、17、18、21和22可以预测放疗治疗后的未来进展。另外，我们 假设侵略性垂体腺瘤和癌港的复发性表观遗传和遗传 定义更具侵略性分子亚型的基因和途径水平的改变。这个基础 需要工作，以便临床医生可以前瞻性地识别具有更高恶性潜力的肿瘤。这 鉴定侵略性疾病的生物标志物对于通过防止两者都能改善患者预后至关重要 过度和不足，以及用于临床试验开发。