Medical Genetics Commons^™

The Molecular Landscape Of Early-Stage Breast Cancer With Lymph Node Metastasis, Farhad Ghasemi

Electronic Thesis and Dissertation Repository

Axillary lymph nodes (ALNs) are the primary site of metastasis in breast cancer, and their involvement has implications in disease staging, prognostication, and treatment decisions. A non-invasive modality of assessing the risk of ALN metastasis can improve care in patients with early-stage breast cancer by omitting the morbidity and costs associated with axillary surgery.

This thesis explores the molecular landscape of early-stage breast cancers with ALN metastasis and shows the potential of tumour molecular signatures in predicting ALN involvement. After a systematic review of the literature, we use data from The Cancer Genome Atlas (TCGA) to develop molecular signatures correlated …

The Experiences And Needs Of Individuals With A Variant Of Uncertain Significance (Vus) On Genetic Tests For Hereditary Cancer Syndromes: A Grounded Theory Study, Danielle Gould

Doctoral Dissertations

Background: The use of multigene panel testing for identifying individuals with hereditary cancer susceptibility has expanded in recent years. The number of individuals who have a variant of unknown significance (VUS) result is increasing. However, little is known about the experiences and needs of this group. This study’s purpose was to describe the experiences and needs of individuals with a VUS result by focusing on their experiences in communicating with healthcare providers and family members. Methods: A constructivist grounded theory approach was used. Recruitment took place from January–July 2021 through social media: the Prospective Registry of Multiplex Testing (PROMPT), and …

Managing Variant Discrepancy In Hereditary Cancer: Clinical Practice, Barriers, And Desired Resources, Ellen Zirkelbach

Dissertations & Theses (Open Access)

Variants are changes in the DNA whose phenotypic effects may or may not be definitively understood. Because variant interpretation is a complex process, sources sometimes disagree on the classification of a variant, which is called a variant discrepancy. This study aimed to determine the practice of genetic counselors regarding variant discrepancies and to identify the barriers to counseling a variant discrepancy in hereditary cancer genetic testing. This investigation was unique because it was the first to address variant discrepancies from a clinical point of view. An electronic survey was sent to genetic counselors in the NSGC Cancer Special Interest Group. …

Anti-Apoptotic Mcl-1 Localizes To The Mitochondrial Matrix And Couples Mitochondrial Fusion To Respiration, Rhonda Perciavalle

Theses and Dissertations (ETD)

MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose cell death, precisely how it functions to promote survival of normal and malignant cells is poorly understood. Here, I report that different forms of MCL-1 reside in distinct mitochondrial locations and exhibit separable functions. On the outer mitochondrial membrane, a MCL-1 isoform acts like other anti-apoptotic BCL-2 molecules to antagonize apoptosis, whereas an amino-terminally truncated isoform of MCL-1 that is imported into the mitochondrial matrix is necessary to …

Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis Using A Breast Cancer Mouse Model, Aiman Alhazmi

Theses and Dissertations

Understanding the impact of epigenetic mechanisms on tumorigenesis is essential, as epigenetic alterations are associated with tumor initiation and progression. Because epigenetic changes are reversible, they are potential targets for cancer therapy. Nucleosome Remodeling Factor (NURF) is a chromatin-remodeling complex that regulates gene expression by changing nucleosome positioning along the DNA sequence. Previous studies have shown a role for NURF in embryonic development as well as regulating genes involved in tumor progression. In this work we investigated the impact of eliminating NURF function in tumorigenesis in vivo. BALB/c mice challenged with syngeneic 67NR breast cancer cell lines, injected into the …

Heat Shock Proteins As Novel Cancer Therapeutics: Targeting The Hallmarks Of Cancer, Chao Li

Theses and Dissertations

Molecular chaperones, commonly known as heat shock proteins (HSPs), are essential for mammalian cells to maintain homeostasis, and HSPs function by inducing an ATPase-coupled structural change, followed by interactions with diverse co-chaperones and over 200 client proteins implicated in many critical signaling networks. These highly expressed HSPs participate in the onset and progression of several human diseases including cancer, and their connection with tumorigenesis has facilitated research and clinical trials related to targeting HSPs as a novel anti-tumor therapy. The predominant mechanism of chaperone inhibition is through either disruption of the HSP association with client protein or an altered binding …

A Critical Review Of Telomerase Biology And Model Systems For The Study Of Telomerase, Jeremy Charles Aisenberg

Theses and Dissertations

The study of telomere and telomerase biology holds substantial promise in uncovering the molecular process of aging and the treatment of cancers. Studies have shown that telomere shortening is directly linked to cellular aging and that telomerase expression is found in over 85% of human cancers, including 95% of all advanced malignancies. Development of effective model systems to elucidate the molecular mechanisms underlying the role of telomeres and telomerase in the processes aging and cancer is of particular importance. While inbred strains of mice have provided a wealth of information for a variety of pathways and diseases, the mouse model …

Dual Regulation Of Telomerase Activity By Hsf1 And Its Role In Prostate Cancer Progression, Keith Douglas Ostergaard Jensen

Theses and Dissertations

It has been shown that the key components of the hsp90 chaperone complex, including hsp90, p23, hsp70, hsp40, and HOP (p60), associate with telomerase; however, their specific roles in telomerase function and tumor progression have not yet been defined. HSF1, the primary mammalian heat shock protein transcription factor, may affect telomerase activity and transformation by regulating the expression of several hsp90 chaperone complex proteins in response to stress as well as regulating the transcription of hTERT, the protein subunit of telomerase.In our in vitro model of prostate cancer progression, as cells progress from immortal but non-tumorigenic (P69) to tumorigenic (M2182) …