Medical Specialties Commons^™

Juvenile Granulosa Cell Tumor In An Adult Woman During Pregnancy: A Case Report And Review Of The Literature, Mackenzie Cummings, Pamela Edmonds, Mark S. Shahin, Joe I. Sorosky

Abington Jefferson Health Papers

Objective

To report a case of stage IIIB juvenile granulosa cell tumor (JGCT) complicating pregnancy in a 33 year-old (y.o.) woman.

Methods

Retrospective review of the clinical data, imaging studies, and pathology reports of a case of JGCT diagnosed during pregnancy. Patient consent was obtained for review and presentation of the case. A literature review was conducted.

Results

A 33 y.o., gravida 3, para 1 was incidentally found to have an 8 cm left ovarian mass on an anatomy scan at 22 weeks gestation. Four days later, she presented to labor and delivery triage with abdominal pain. An ultrasound revealed …

Endovascular Image-Guided Sampling Of Tumor-Draining Veins Provides An Enriched Source Of Oncological Biomarkers, Anobel Tamrazi, Srividya Sundaresan, Aishwarya Gulati, Frederick J. Tan, Vibhor Wadhwa, Bjarne R. Bartlett, Luis A. Diaz Jr.

Department of Radiology Faculty Papers

Introduction: Circulating tumor-derived biomarkers can potentially impact cancer management throughout the continuum of care. This small exploratory study aimed to assess the relative levels of such biomarkers in the tumor-draining vascular beds in patients with solid tumors compared to levels in their peripheral veins.

Methods: Using an endovascular image-guided approach, we obtained blood samples from peripheral veins and other vascular compartments–including the most proximal venous drainage from solid tumors–from a set of nine oncology patients with various primary and metastatic malignancies. We then interrogated these samples for a panel of oncological biomarkers, including circulating tumor cells (CTCs), exosome-derived microRNAs (miRNAs), …

Protocols For Single-Cell Rna-Seq And Spatial Gene Expression Integration And Interactive Visualization, Surbhi Sona, Matthew Bradley, Angela H Ting

Faculty, Staff and Student Publications

There is a wealth of software that utilizes single-cell RNA-seq (scRNA-seq) data to deconvolve spatial transcriptomic spots, which currently are not yet at single-cell resolution. Here we provide protocols for implementing Seurat and Giotto packages to elucidate cell-type distribution in our example human ureter scRNA-seq dataset. We also describe how to create a stand-alone interactive web application using Seurat libraries to visualize and share our results. For complete details on the use and execution of this protocol, please refer to Fink et al. (2022).

Apkcs Role In Neuroblastoma Cell Signaling Cascades And Implications Of Apkcs Inhibitors As Potential Therapeutics, Sloan Breedy

USF Tampa Graduate Theses and Dissertations

Neuroblastoma (NB) is a cancer that develops in the neuroblasts. It is the most common cancer in children under the age of 1 year, accounting for approximately 6% of all cancers. The prognosis of NB is linked to both age and degree of cell differentiation. This results in a range of survival rates for patients, with outcomes ranging from recurrence and mortality to high survival rates and tumor regression. Our previous work indicated that PKC-ι promotes cell proliferation in NB cells through the PKC-ι/Cdk7/Cdk2 cascade. We report on two atypical protein kinase inhibitors as potential therapeutic candidates against BE(2)-C and …

A Mast Cell-Thermoregulatory Neuron Circuit Axis Regulates Hypothermia In Anaphylaxis, Chunjing Bao, Ouyang Chen, Huaxin Sheng, Jeffrey Zhang, Yikai Luo, Byron W Hayes, Han Liang, Wolfgang Liedtke, Ru-Rong Ji, Soman N Abraham

Faculty, Staff and Student Publications

IgE-mediated anaphylaxis is an acute life-threatening systemic reaction to allergens, including certain foods and venoms. Anaphylaxis is triggered when blood-borne allergens activate IgE-bound perivascular mast cells (MCs) throughout the body, causing an extensive systemic release of MC mediators. Through precipitating vasodilatation and vascular leakage, these mediators are believed to trigger a sharp drop in blood pressure in humans and in core body temperature in animals. We report that the IgE/MC-mediated drop in body temperature in mice associated with anaphylaxis also requires the body's thermoregulatory neural circuit. This circuit is activated when granule-borne chymase from MCs is deposited on proximal TRPV1+ …

Comparison Of Four Clinical Prognostic Scores In Patients With Advanced Gastric And Esophageal Cancer, Lucy X Ma, Osvaldo Espin-Garcia, Yvonne Bach, Hiroko Aoyama, Michael J Allen, Xin Wang, Gail E Darling, Jonathan Yeung, Carol J Swallow, Savtaj Brar, Patrick Veit-Haibach, Sangeetha Kalimuthu, Rebecca Wong, Eric X Chen, Grainne M O'Kane, Raymond W Jang, Elena Elimova

Faculty, Staff and Student Publications

Background: Prognostic scores that can identify patients at risk for early death are needed to aid treatment decision-making and patient selection for clinical trials. We compared the accuracy of four scores to predict early death (within 90 days) and overall survival (OS) in patients with metastatic gastric and esophageal (GE) cancer.

Methods: Advanced GE cancer patients receiving first-line systemic therapy were included. Prognostic risks were calculated using: Royal Marsden Hospital (RMH), MD Anderson Cancer Centre (MDACC), Gustave Roussy Immune (GRIm-Score), and MD Anderson Immune Checkpoint Inhibitor (MDA-ICI) scores. Overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazards …

A Differentiation Roadmap Of Murine Placentation At Single-Cell Resolution, Xiangxiang Jiang, Yue Wang, Zhenyu Xiao, Long Yan, Shanshan Guo, Yiming Wang, Hao Wu, Xuehan Zhao, Xiaoyin Lu, Hongmei Wang

Faculty, Staff and Student Publications

The placenta is one of the most important yet least understood organs. Due to the limitations of conventional research approaches, we are still far from a comprehensive understanding of mouse placentation, especially regarding the differentiation of trophoblast lineages at the early developmental stage. To decipher cell compositions and developmental processes, we systematically profile the single-cell transcriptomes of trophoblast cells from extraembryonic tissues (embryonic day 7.5 (E7.5) and E8.5) and placentae (E9.5-E14.5) at one-day intervals. We identify distinct trophoblast cell types during mouse placentation, including unreported progenitor cells and intermediate precursor cells. An updated differentiation roadmap of mouse trophoblast lineages is …

Ferroptosis Hijacking By Mycobacterium Tuberculosis, Boyi Gan

Faculty, Staff and Student Publications

A recent study from Nature Communications reveals that Mycobacterium tuberculosis can hijack epigenetic machinery in host cells and induce host cell ferroptosis, which promotes pathogen pathogenicity and spread. These findings also suggest new therapeutic strategies to treat tuberculosis.

Hervs And Cancer-A Comprehensive Review Of The Relationship Of Human Endogenous Retroviruses And Human Cancers, Erik Stricker, Erin C Peckham-Gregory, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

Genomic instability and genetic mutations can lead to exhibition of several cancer hallmarks in affected cells such as sustained proliferative signaling, evasion of growth suppression, activated invasion, deregulation of cellular energetics, and avoidance of immune destruction. Similar biological changes have been observed to be a result of pathogenic viruses and, in some cases, have been linked to virus-induced cancers. Human endogenous retroviruses (HERVs), once external pathogens, now occupy more than 8% of the human genome, representing the merge of genomic and external factors. In this review, we outline all reported effects of HERVs on cancer development and discuss the HERV …

Young Adult Cancer Patients And Survivors’ Adherence To Healthy Eating And Physical Activity Guidelines, Sandra Soca Lozano

USF Tampa Graduate Theses and Dissertations

Many Adolescents and Young Adult (AYA) cancer patients/survivors do not engage in healthy eating and physical activity recommendations. The present study assessed the role of race/ethnicity, health literacy, and home environmental influences and its association with adherence to healthy eating and physical activity. AYA patients/survivors from Moffitt Cancer Center (n = 273) completed an anonymous online survey. Self-reported measures about eating habits, physical activity, health literacy, and social support were used. Black/African Americans reported worse eating habits than White and Hispanic participants. Obese participants showed a similar trend compared to all other Body Mass Index groups. Adherence to physical activity …

How Erastin Assassinates Cells By Ferroptosis Revealed, Boyi Gan

Faculty, Staff and Student Publications

No abstract provided.

Esrage-Expressing Ohsv Enhances Anti-Tumor Efficacy By Inhibition Of Endothelial Cell Activation, Jessica Swanner, Ji Seon Shim, Kimberly A Rivera-Caraballo, Karina Vázquez-Arreguín, Bangxing Hong, Alberto J Bueso-Perez, Tae Jin Lee, Yeshavanth Kumar Banasavadi-Siddegowda, Balveen Kaur, Ji Young Yoo

Faculty, Staff and Student Publications

High-mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule that plays an important role in inflammation and tumorigenesis. Receptor for advanced glycation end products (RAGE) is one of the major receptors to which extracellular HMGB1 binds to mediate its activity. RAGE is highly expressed on the endothelial cells (ECs) and regulates endothelial permeability during inflammation. Here, we introduced the endogenous secretory form of RAGE (esRAGE) as a decoy receptor for RAGE ligands into an oncolytic herpes simplex virus 1 (oHSV) (OVesRAGE), which, upon release, can function to block RAGE signaling. OVesRAGE significantly decreased phosphorylation of MEK1/2 and …

Factors Associated With Open Access Publishing Costs In Oncology Journals: Cross-Sectional Observational Study, Alex Koong, Ulysses Grant Gardner, Jason Burton, Caleb Stewart, Petria Thompson, Clifton David Fuller, Ethan Bernard Ludmir, Michael Kevin Rooney

Faculty, Staff and Student Publications

Background: Open access (OA) publishing represents an exciting opportunity to facilitate the dissemination of scientific information to global audiences. However, OA publishing is often associated with significant article processing charges (APCs) for authors, which may thus serve as a barrier to publication.

Objective: In this observational cohort study, we aimed to characterize the landscape of OA publishing in oncology and, further, identify characteristics of oncology journals that are predictive of APCs.

Methods: We identified oncology journals using the SCImago Journal & Country Rank database. All journals with an OA publication option and APC data openly available were included. We searched …

Venetoclax And Idasanutlin In Relapsed/Refractory Aml: A Nonrandomized, Open-Label Phase 1b Trial, Naval G Daver, Monique Dail, Jacqueline S Garcia, Brian A Jonas, Karen W L Yee, Kevin R Kelly, Norbert Vey, Sarit Assouline, Gail J Roboz, Stefania Paolini, Daniel A Pollyea, Agostino Tafuri, Joseph M Brandwein, Arnaud Pigneux, Bayard L Powell, Pierre Fenaux, Rebecca L Olin, Giuseppe Visani, Giovanni Martinelli, Maika Onishi, Jue Wang, Weize Huang, Cherie Green, Marion G Ott, Wan-Jen Hong, Marina Y Konopleva, Michael Andreeff

Faculty, Staff and Student Publications

This phase 1b trial (NCT02670044) evaluated venetoclax-idasanutlin in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) ineligible for cytotoxic chemotherapy. Two-dimensional dose escalation (DE, n = 50) was performed for venetoclax daily with idasanutlin on days 1 to 5 in 28-day cycles, followed by dosing schedule optimization (n = 6) to evaluate reduced venetoclax schedules (21-/14-day dosing). Common adverse events (occurring in ≥40% of patients) included diarrhea (87.3% of patients), nausea (74.5%), vomiting (52.7%), hypokalemia (50.9%), and febrile neutropenia (45.5%). During DE, across all doses, composite complete remission (CRc; CR + CR with incomplete blood count recovery + CR with …

The Evolution Of Acute Lymphoblastic Leukemia Research And Therapy At Md Anderson Over Four Decades, Elias Jabbour, Nicholas J Short, Nitin Jain, Fadi G Haddad, Mary Alma Welch, Farhad Ravandi, Hagop Kantarjian

Faculty, Staff and Student Publications

Progress in the research and therapy of adult acute lymphoblastic leukemia (ALL) is accelerating. This analysis summarizes the data derived from the clinical trials conducted at MD Anderson between 1985 and 2022 across ALL subtypes. In Philadelphia chromosome-positive ALL, the addition of BCR::ABL1 tyrosine kinase inhibitors (TKIs) to intensive chemotherapy since 2000, improved outcomes. More recently, a chemotherapy-free regimen with blinatumomab and ponatinib resulted in a complete molecular remission rate of 85% and an estimated 3-year survival rate of 90%, potentially reducing the role of, and need for allogeneic stem cell transplantation (SCT) in remission. In younger patients with pre-B …

Animal Models And Their Role In Imaging-Assisted Co-Clinical Trials, Donna M Peehl, Cristian T Badea, Thomas L Chenevert, Heike E Daldrup-Link, Li Ding, Lacey E Dobrolecki, A Mcgarry Houghton, Paul E Kinahan, John Kurhanewicz, Michael T Lewis, Shunqiang Li, Gary D Luker, Cynthia X Ma, H Charles Manning, Yvonne M Mowery, Peter J O'Dwyer, Robia G Pautler, Mark A Rosen, Raheleh Roudi, Brian D Ross, Kooresh I Shoghi, Renuka Sriram, Moshe Talpaz, Richard L Wahl, Rong Zhou

Faculty, Staff and Student Publications

The availability of high-fidelity animal models for oncology research has grown enormously in recent years, enabling preclinical studies relevant to prevention, diagnosis, and treatment of cancer to be undertaken. This has led to increased opportunities to conduct co-clinical trials, which are studies on patients that are carried out parallel to or sequentially with animal models of cancer that mirror the biology of the patients' tumors. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are considered to be the models that best represent human disease and have high translational value. Notably, one element of co-clinical trials that still needs significant …

Safety Of Nivolumab Added To Chemoradiation Therapy Platforms For Intermediate And High-Risk Locoregionally Advanced Head And Neck Squamous Cell Carcinoma: Rtog Foundation 3504, Maura L Gillison, Robert L Ferris, Jonathan Harris, A Dimitrios Colevas, Loren K Mell, Christina Kong, Richard C Jordan, Kevin L Moore, Minh-Tam Truong, Claudia Kirsch, Arnab Chakravarti, Dukagjin M Blakaj, David A Clump, James P Ohr, John F Deeken, Michael F Gensheimer, Nabil F Saba, Jennifer A Dorth, David I Rosenthal, Rom S Leidner, Randall J Kimple, Mitchell Machtay, Walter J Curran, Pedro Torres-Saavedra, Quynh Thu Le

Faculty, Staff and Student Publications

PURPOSE: Programmed death-1 immune checkpoint blockade improves survival of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but the benefits of addition to (chemo)radiation for newly diagnosed patients with HNSCC remain unknown.

METHODS AND MATERIALS: We evaluated the safety of nivolumab concomitant with 70 Gy intensity modulated radiation therapy and weekly cisplatin (arm 1), every 3-week cisplatin (arm 2), cetuximab (arm 3), or alone for platinum-ineligible patients (arm 4) in newly diagnosed intermediate- or high-risk locoregionally advanced HNSCC. Patients received nivolumab from 2 weeks prior to radiation therapy until 3 months post-radiation therapy. The primary endpoint was dose-limiting …

The Alpha7 Integrin Subunit In Astrocytes Promotes Endothelial Blood-Brain Barrier Integrity, Zhihua Chen, Jack R Kelly, John E Morales, Raymond C Sun, Arpan De, Dean J Burkin, Joseph H Mccarty

Faculty, Staff and Student Publications

The blood-brain barrier (BBB) is a vascular endothelial cell boundary that partitions the circulation from the central nervous system to promote normal brain health. We have a limited understanding of how the BBB is formed during development and maintained in adulthood. We used quantitative transcriptional profiling to investigate whether specific adhesion molecules are involved in BBB functions, with an emphasis on understanding how astrocytes interact with endothelial cells. Our results reveal a striking enrichment of multiple genes encoding laminin subunits as well as the laminin receptor gene Itga7, which encodes the alpha7 integrin subunit, in astrocytes. Genetic ablation of Itga7 …

Sequential Targeting Of Retinoblastoma And Dna Synthesis Pathways Is A Therapeutic Strategy For Sarcomas That Can Be Monitored In Real Time, Tuyen Duong Thanh Nguyen, Yan Wang, Tuyen N Bui, Rossana Lazcano, Davis R Ingram, Min Yi, Varshini Vakulabharanam, Linjie Luo, Marc A Pina, Cansu Karakas, Mi Li, Nicole M Kettner, Neeta Somaiah, Peter J Hougton, Osama Mawlawi, Alexander J Lazar, Kelly K Hunt, Khandan Keyomarsi

Faculty, Staff and Student Publications

Treatment strategies with a strong scientific rationale based on specific biomarkers are needed to improve outcomes in patients with advanced sarcomas. Suppression of cell cycle progression through reactivation of the tumor suppressor retinoblastoma (Rb) using CDK4/6 inhibitors is a potential avenue for novel targeted therapies in sarcomas that harbor intact Rb signaling. Here, we evaluated combination treatment strategies (sequential and concomitant) with the CDK4/6 inhibitor abemacicib to identify optimal combination strategies. Expression of Rb was examined in 1043 sarcoma tumor specimens, and 50% were found to be Rb-positive. Using in vitro and in vivo models, an effective 2-step sequential combination …

Etnk1 Mutation Occurs In A Wide Spectrum Of Myeloid Neoplasms And Is Not Specific For Atypical Chronic Myeloid Leukemia, Wen Shuai, Zhuang Zuo, Nianyi Li, Sofia Garces, Fatima Zahra Jelloul, Chi Young Ok, Shaoying Li, Jie Xu, M James You, Wei Wang, Catherine Rehder, Elias J Jabbour, Keyur P Patel, L Jeffrey Medeiros, C Cameron Yin

Faculty, Staff and Student Publications

Background: ETNK1 mutation has been suggested as a useful tool to support the diagnosis of atypical chronic myeloid leukemia. ETNK1 mutations, however, occur in other myeloid neoplasms.

Methods: The authors assessed the clinicopathologic and molecular genetic features of 80 ETNK1-mutated myeloid neoplasms.

Results: Thirty-seven neoplasms (46%) were classified as myelodysplastic syndrome, 17 (21%) were classified as myelodysplastic/myeloproliferative neoplasm, 14 (18%) were classified as acute myeloid leukemia, and 12 (15%) were classified as myeloproliferative neoplasm. ETNK1 mutations were detected at the first test in 96% of patients, suggesting that ETNK1 mutation is an early event in pathogenesis. ETNK1 mutations represented the …

Kdm6a Loss Triggers An Epigenetic Switch That Disrupts Urothelial Differentiation And Drives Cell Proliferation In Bladder Cancer, Hong Qiu, Vladimir Makarov, Jennifer K Bolzenius, Angela Halstead, Yvonne Parker, Allen Wang, Gopakumar V Iyer, Hannah Wise, Daniel Kim, Varna Thayaparan, Daniel J Lindner, Georges-Pascal Haber, Angela H Ting, Bing Ren, Timothy A Chan, Vivek Arora, David B Solit, Byron H Lee

Faculty, Staff and Student Publications

Disruption of KDM6A, a histone lysine demethylase, is one of the most common somatic alternations in bladder cancer. Insights into how KDM6A mutations affect the epigenetic landscape to promote carcinogenesis could help reveal potential new treatment approaches. Here, we demonstrated that KDM6A loss triggers an epigenetic switch that disrupts urothelial differentiation and induces a neoplastic state characterized by increased cell proliferation. In bladder cancer cells with intact KDM6A, FOXA1 interacted with KDM6A to activate genes instructing urothelial differentiation. KDM6A-deficient cells displayed simultaneous loss of FOXA1 target binding and genome-wide redistribution of the bZIP transcription factor ATF3, which in turn repressed …

Sequential Targeting Of Retinoblastoma And Dna Synthesis Pathways Is A Therapeutic Strategy For Sarcomas That Can Be Monitored In Real Time, Tuyen Duong Thanh Nguyen, Yan Wang, Tuyen N Bui, Rossana Lazcano, Davis R Ingram, Min Yi, Varshini Vakulabharanam, Linjie Luo, Marc A Pina, Cansu Karakas, Mi Li, Nicole M Kettner, Neeta Somaiah, Peter J Hougton, Osama Mawlawi, Alexander J Lazar, Kelly K Hunt, Khandan Keyomarsi

Faculty, Staff and Student Publications

Treatment strategies with a strong scientific rationale based on specific biomarkers are needed to improve outcomes in patients with advanced sarcomas. Suppression of cell-cycle progression through reactivation of the tumor suppressor retinoblastoma (Rb) using CDK4/6 inhibitors is a potential avenue for novel targeted therapies in sarcomas that harbor intact Rb signaling. Here, we evaluated combination treatment strategies (sequential and concomitant) with the CDK4/6 inhibitor abemacicib to identify optimal combination strategies. Expression of Rb was examined in 1,043 sarcoma tumor specimens, and 50% were found to be Rb-positive. Using in vitro and in vivo models, an effective two-step sequential combination strategy …

T-Cell Receptor Repertoire Sequencing In The Era Of Cancer Immunotherapy, Meredith L Frank, Kaylene Lu, Can Erdogan, Yi Han, Jian Hu, Tao Wang, John V Heymach, Jianjun Zhang, Alexandre Reuben

Faculty, Staff and Student Publications

T cells are integral components of the adaptive immune system, and their responses are mediated by unique T-cell receptors (TCR) that recognize specific antigens from a variety of biological contexts. As a result, analyzing the T-cell repertoire offers a better understanding of immune responses and of diseases like cancer. Next-generation sequencing technologies have greatly enabled the high-throughput analysis of the TCR repertoire. On the basis of our extensive experience in the field from the past decade, we provide an overview of TCR sequencing, from the initial library preparation steps to sequencing and analysis methods and finally to functional validation techniques. …

Genetic Architecture Of Spatial Electrical Biomarkers For Cardiac Arrhythmia And Relationship With Cardiovascular Disease, William J Young, Jeffrey Haessler, Jan-Walter Benjamins, Linda Repetto, Jie Yao, Aaron Isaacs, Andrew R Harper, Julia Ramirez, Sophie Garnier, Stefan Van Duijvenboden, Antoine R Baldassari, Maria Pina Concas, Thuyvy Duong, Luisa Foco, Jonas L Isaksen, Hao Mei, Raymond Noordam, Casia Nursyifa, Anne Richmond, Meddly L Santolalla, Colleen M Sitlani, Negin Soroush, Sébastien Thériault, Stella Trompet, Stefanie Aeschbacher, Fariba Ahmadizar, Alvaro Alonso, Jennifer A Brody, Archie Campbell, Adolfo Correa, Dawood Darbar, Antonio De Luca, Jean-François Deleuze, Christina Ellervik, Christian Fuchsberger, Anuj Goel, Christopher Grace, Xiuqing Guo, Torben Hansen, Susan R Heckbert, Rebecca D Jackson, Jan A Kors, Maria Fernanda Lima-Costa, Allan Linneberg, Peter W Macfarlane, Alanna C Morrison, Pau Navarro, David J Porteous, Peter P Pramstaller, Alexander P Reiner, Lorenz Risch, Ulrich Schotten, Xia Shen, Gianfranco Sinagra, Elsayed Z Soliman, Monika Stoll, Eduardo Tarazona-Santos, Andrew Tinker, Katerina Trajanoska, Eric Villard, Helen R Warren, Eric A Whitsel, Kerri L Wiggins, Dan E Arking, Christy L Avery, David Conen, Giorgia Girotto, Niels Grarup, Caroline Hayward, J Wouter Jukema, Dennis O Mook-Kanamori, Morten Salling Olesen, Sandosh Padmanabhan, Bruce M Psaty, Cristian Pattaro, Antonio Luiz P Ribeiro, Jerome I Rotter, Bruno H Stricker, Pim Van Der Harst, Cornelia M Van Duijn, Niek Verweij, James G Wilson, Michele Orini, Philippe Charron, Hugh Watkins, Charles Kooperberg, Henry J Lin, James F Wilson, Jørgen K Kanters, Nona Sotoodehnia, Borbala Mifsud, Pier D Lambiase, Larisa G Tereshchenko, Patricia B Munroe

Faculty, Staff and Student Publications

The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic …

Renal Cell Carcinoma Unclassified With Medullary Phenotype In A Patient With Neurofibromatosis Type 2, Sanila Sarkar, Whitney Throckmorton, Racheal Bingham, Pavlos Msaouel, Giannicola Genovese, John Slopis, Priya Rao, Zsila Sadighi, Cynthia E Herzog

Faculty, Staff and Student Publications

We present, to our knowledge, the first reported case of germline neurofibromatosis Type 2 (NF2) associated with renal cell carcinoma unclassified with medullary phenotype (RCCU-MP) with somatic loss by immunohistochemistry of the SMARCB1 tumor suppressor gene located centromeric to NF2 on chromosome 22q. Our patient is a 15-year-old with germline neurofibromatosis Type 2 (NF2) confirmed by pathogenic mutation of c.-854-??46+??deletion. Her NF2 history is positive for a right optic nerve sheath meningioma, CNIII schwannoma requiring radiation therapy and post gross total resection of right frontotemporal anaplastic meningioma followed by radiation. At age 15 she developed new onset weight loss and …

Enzalutamide-Induced Signatures Revealed By Epigenetic Plasticity Using Single-Cell Multi-Omics Sequencing In Prostate Cancer, Huihui Fan, Jinze Li, Astrid M Manuel, Zhongming Zhao

Faculty, Staff and Student Publications

Prostate cancer is morphologically and molecularly heterogeneous, which poses obstacles for early diagnosis and treatment. Advancements in understanding the heterogeneity of prostate cancer will help navigate through these challenges and ultimately benefit patients. In this study, we integrated single-cell sequencing for transposase-accessible chromatin and whole transcriptome in prostate cancer cell lines, aiming to decode the epigenetic plasticity upon enzalutamide (ENZ) treatment. By comparing the cell populations representing early-treatment response or resistance to the initial tumor cells, we identified seven signature gene sets; they present consistent trends of chromatin closing co-occurred with down-regulated genes during early response and chromatin opening with …

Validation Of The Alfa-1200 Model In Older Patients With Aml Treated With Intensive Chemotherapy, Hussein A Abbas, Hanxiao Sun, Sherry Pierce, Rashmi Kanagal-Shamanna, Ziyi Li, Musa Yilmaz, Gautam Borthakur, Adam J Dipippo, Elias Jabbour, Marina Konopleva, Nicholas J Short, Courtney Dinardo, Naval Daver, Farhad Ravandi, Tapan M Kadia

Faculty, Staff and Student Publications

No abstract provided.

Hypermitotic Meningiomas Harbor Dna Methylation Subgroups With Distinct Biological And Clinical Features, Abrar Choudhury, William C Chen, Calixto-Hope G Lucas, James C Bayley, Akdes S Harmanci, Sybren L N Maas, Sandro Santagata, Tiemo Klisch, Arie Perry, Wenya Linda Bi, Felix Sahm, Akash J Patel, Stephen T Magill, David R Raleigh

Faculty, Staff and Students Publications

BACKGROUND: Meningiomas, the most common primary intracranial tumors, can be separated into 3 DNA methylation groups with distinct biological drivers, clinical outcomes, and therapeutic vulnerabilities. Alternative meningioma grouping schemes using copy number variants, gene expression profiles, somatic short variants, or integrated molecular models have been proposed. These data suggest meningioma DNA methylation groups may harbor subgroups unifying contrasting theories of meningioma biology.

METHODS: A total of 565 meningioma DNA methylation profiles from patients with comprehensive clinical follow-up at independent discovery (n = 200) or validation (n = 365) institutions were reanalyzed and classified into Merlin-intact, Immune-enriched, or Hypermitotic DNA methylation …

Prognostication Of Dna Damage Response Protein Expression Patterns In Chronic Lymphocytic Leukemia, Ti'ara L Griffen, Fieke W Hoff, Yihua Qiu, Jan Burger, William Wierda, Steven M Kornblau

Faculty, Staff and Student Publications

Proteomic DNA Damage Repair (DDR) expression patterns in Chronic Lymphocytic Leukemia were characterized by quantifying and clustering 24 total and phosphorylated DDR proteins. Overall, three protein expression patterns (C1-C3) were identified and were associated as an independent predictor of distinct patient overall survival outcomes. Patients within clusters C1 and C2 had poorer survival outcomes and responses to fludarabine, cyclophosphamide, and rituxan chemotherapy compared to patients within cluster C3. However, DDR protein expression patterns were not prognostic in more modern therapies with BCL2 inhibitors or a BTK/PI3K inhibitor. Individually, nine of the DDR proteins were prognostic for predicting overall survival and/or …

Reverse Phase Protein Array Profiling Identifies Recurrent Protein Expression Patterns Of Dna Damage-Related Proteins Across Acute And Chronic Leukemia: Samples From Adults And The Children's Oncology Group, Fieke W Hoff, Ti'ara L Griffen, Brandon D Brown, Terzah M Horton, Jan Burger, William Wierda, Stefan E Hubner, Yihua Qiu, Steven M Kornblau

Faculty, Staff and Student Publications

DNA damage response (DNADR) recognition and repair (DDR) pathways affect carcinogenesis and therapy responsiveness in cancers, including leukemia. We measured protein expression levels of 16 DNADR and DDR proteins using the Reverse Phase Protein Array methodology in acute myeloid (AML) (n = 1310), T-cell acute lymphoblastic leukemia (T-ALL) (n = 361) and chronic lymphocytic leukemia (CLL) (n = 795) cases. Clustering analysis identified five protein expression clusters; three were unique compared to normal CD34+ cells. Individual protein expression differed by disease for 14/16 proteins, with five highest in CLL and nine in T-ALL, and by age in …