Open Access Senior Thesis
Bachelor of Arts
2022 Grace Z. Zhang
Pituitary neuroendocrine tumors (PitNETs) are tumors of the pituitary gland. Although most are benign, they can cause severe morbidity if compression of surrounding tissue and/or endocrinopathies occur.
Aggressive PitNETs are notably detrimental and difficult to predict, and their effects are further exacerbated by challenges in treatment. Although histological studies can detect certain markers of tumor aggressiveness, they are insufficient at wholly predicting PitNET aggressiveness, making the clinical behavior of PitNETs challenging to determine. Since treatment of aggressive tumors also remains suboptimal, this further results in negative impacts on health and quality of life.
Genetic markers, such as copy number variations (CNVs), could be particularly powerful in detecting PitNET aggressiveness prior to the manifestation of clinical signs of tumor progression. If CNVs are a biomarker for aggressive PitNETs, this would greatly improve their diagnosis and treatment process.
To identify whether CNVs predict PitNET aggressiveness, this retrospective study examined clinical and genetic features of non-functional (NF) PitNETs, prolactinomas, corticotropinomas, and somatotropinomas. DNA extraction and quantification of PitNETs was performed. Pituitary DNA that had undergone whole-genome sequencing (WGS) was previously analyzed for CNVs and data extraction of the respective PitNET patients’ clinical charts was performed. Features of clinical aggressiveness were compared to the CNV data. It was found that PitNETs with copy number gains were the most clinically aggressive, and that the subtypes of PitNETs arose from different combinations of copy number gains and losses on different chromosomes. These findings likely reflect results from recently collected pituitary tumor and blood DNA sent for whole-genome sequencing. This research supports that aggressive PitNETs can be identified by CNVs and suggests that subtypes of aggressive PitNETs arise from different tumor suppressor genes and oncogenes, which supports the notion that PitNETs are heterogeneous. Knowledge of aggressive PitNET heterogeneity would ultimately allow for more effective diagnosis and treatment for aggressive PitNETs.
Zhang, Grace, "Copy Number Alterations of Aggressive Pituitary Neuroendocrine Tumors" (2023). Scripps Senior Theses. 2139.