Document text
Principal Investigator: Andrew Lin
Organization: SLOAN-KETTERING INST CAN RESEARCH
Fiscal Year: 2024
Award: $196,525
Funding agency: National Cancer Institute
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.
Terms: <Abscission><Active Follow-up><Address><Adenohypophysis><Adrenocorticotropin Producing Pituitary Adenoma><Adrenocorticotropin Producing Pituitary Gland Adenoma><Adrenocorticotropin Secreting Pituitary Adenoma><Adrenocorticotropin Secreting Pituitary Gland Adenoma><Aggression><Aggressive behavior><Algorithms><Alkylating Agents Chemotherapy><Alkylating Antineoplastic Agents><Alkylating Antineoplastic Drugs><Alkylating Antineoplastics><Anterior Pituitary Gland><Anterior pituitary><Askenazy Cells><Autopsy><Basicranium><Basis cranii><Behavior><Benign><Biological Markers><Blindness><Brain><Brain Neoplasia><Brain Neoplasms><Brain Nervous System><Brain Tumors><Cancers><Carcinoma Cell><Characteristics><Chemotherapy Alkylators><Chromosomal Loss><Chromosomes><Clinical><Clinical Trials><Clonality><Communities><Consent><Copy Number Polymorphism><Corticotroph Adenoma><Corticotropinoma><Cranial Base><DNA methylation profiling><Data><Data Set><Development><Diagnosis><Disease><Disease Progression><Disorder><Encephalon><Endocrine Therapy><Endocrinologist><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Excision><Exhibits><Extirpation><Future><Generalized Growth><Genes><Genetic><Genetic Alteration><Genetic Change><Genetic defect><Genome><Genomics><Goals><Growth><Hormonal Therapy><Hurthle Cells><Incidence><Individual><Indolent><Institution><Intracranial Central Nervous System Neoplasms><Intracranial Central Nervous System Tumors><Intracranial Neoplasms><Intracranial Tumor><Invaded><Island Cell Tumor><Islet Cell Neoplasm><Islet Cell Tumor><Life><Malignant><Malignant - descriptor><Malignant Epithelial Cell><Malignant Neoplasms><Malignant Tumor><Metastasis><Metastasize><Metastatic Lesion><Metastatic Mass><Metastatic Neoplasm><Metastatic Tumor><Methyl-Seq><MethylSeq><Methylation><Methylation sequencing><Molecular><Morbidity><Morbidity - disease rate><Mutation><NCI Organization><NGS Method><NGS system><National Cancer Institute><Natural History><Neoplasm Metastasis><Neuroendocrine Neoplasm><Neuroendocrine Tumors><Neurologic Dysfunctions><Noise><Operative Procedures><Operative Surgical Procedures><Oral><PanNets><Pancreatic Endocrine Neoplasm><Pancreatic Endocrine Tumor><Pancreatic Neuroendocrine Tumor><Pars Anterior Pituitary Gland><Pathway interactions><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pattern><Phenotype><Pituitary ACTH-Secreting Adenoma><Pituitary Adenoma><Pituitary Corticotropin Secreting Adenoma><Pituitary Gland ACTH-Secreting Adenoma><Pituitary Gland Adenoma><Pituitary Gland Carcinoma><Pituitary Gland Neoplasm><Pituitary Gland Tumor><Pituitary Neoplasms><Pituitary Tumors><Pituitary carcinoma><Prevalence><Radiation><Radiation therapy><Radiotherapeutics><Radiotherapy><Recurrence><Recurrent><Registries><Removal><Reporting><SEER Program><SEER-Surveillance, Epidemiology, and End Results><Sampling><Secondary Neoplasm><Secondary Tumor><Subgroup><Surgical><Surgical Interventions><Surgical Procedure><Surgical Removal><Surveillance, Epidemiology and End Results><Surveillance, Epidemiology, and End Results Program><Temodal><Temodar><Time><Tissue Growth><Tumor Bank><United States><Validation><Work><World Health Organization><active followup><adenoma><bio-markers><biologic marker><biomarker><biomarker validation><cancer metastasis><clinical decision-making><clinical phenotype><clinical relevance><clinically relevant><cohort><copy number variant><copy number variation><density><developmental><epigenetically><exome sequencing><exome-seq><expression subtypes><follow up><follow-up><followed up><followup><genome mutation><high risk><hormone therapy><improved><lactotroph><malignancy><marker validation><men><methazolastone><molecular biomarker><molecular marker><molecular sub-types><molecular subsets><molecular subtypes><mortality><necropsy><neoplasm/cancer><neurological dysfunction><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next gen sequencing><next generation sequencing><next generation therapeutics><nextgen sequencing><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><ontogeny><pancreatic NET><pancreatic islet neoplasm><pathway><patient oriented outcomes><pituitary anterior lobe><pituitary gland anterior lobe><postmortem><predictive biomarkers><predictive marker><predictive molecular biomarker><prevent><preventing><prospective><radiation treatment><rapid growth><resection><response><skull base><standard care><standard of care><standard treatment><surgery><temozolomide><treatment with radiation><tumor><tumor cell metastasis><tumor registry><tumors in the brain><validations><vision loss><visual loss>