Medical Specialties Commons^™

Bringing Car T Cell Therapy Trials To Underserved Populations, Hoda Badr, Rayne Rouce, Michael E Scheurer, Premal Lulla, Martha Mims, Pavan Reddy

Faculty, Staff and Students Publications

There is a critical need for equitable access to cell therapies in cancer treatment, particularly within public safety-net healthcare systems that serve minority and socioeconomically disadvantaged populations. We discuss how the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine is piloting a cell therapy program aimed at addressing cancer care disparities and has the potential to serve as a national model for enhancing health equity in cancer care.

Early Surgical Stabilization Of Rib Fractures (Ssrf) Is Better, But Delayed Ssrf Is Not Worse, Stephen J. Bordes, Patrick Greiffenstein

School of Medicine Faculty Publications

Comment on; Belaroussi Y, Drevet G, Soldea V, et al. When to proceed to surgical rib fixation?-A single-institution clinical experience. J Thorac Dis 2023;15;323-34.

Taxane-Based Chemotherapy Is Effective In Metastatic Appendiceal Adenocarcinoma, Julia Dansby, Aditya More, Mohammad Zeineddine, Abdelrahman Yousef, Alisha Bent, Farshid Dayyani, Robert Wolff, Michael Overman, John Paul Shen

Faculty, Staff and Student Publications

Appendiceal cancer is a rare, orphan disease with no therapies currently approved by the FDA for its treatment. Given the limited data regarding drug efficacy, these tumors have historically been treated with chemotherapy designed for colon cancer. However, an overwhelming body of molecular data has demonstrated that appendiceal adenocarcinoma is a distinct entity with key molecular differences from colon cancer, notably rare APC mutation. Recognizing that APC loss-of-function is thought to contribute to taxane resistance and that taxanes are effective in the treatment of other gastrointestinal tumors, including gastric, esophageal, and small bowel adenocarcinoma, we completed a single-center retrospective study …

Sustained Disease Control In Immune Checkpoint Blockade Responders With Microsatellite Instability-High Colorectal Cancer After Treatment Termination, Kristen Simmons, Jane V Thomas, Kaysia Ludford, Jason A Willis, Victoria S Higbie, Kanwal P S Raghav, Benny Johnson, Arvind Dasari, Bryan K Kee, Christine M Parseghian, Michael S Lee, Phat H Le, Maria P Morelli, John Paul Shen, Alisha Bent, Eduardo Vilar, Robert A Wolff, Scott Kopetz, Michael J Overman, Van Karlyle Morris

Faculty, Staff and Student Publications

Immune checkpoint inhibitors improve survival in patients with mismatch repair deficiency/microsatellite instability-high (MSI-H) colorectal cancer. The recurrence outcomes following discontinuation of immunotherapy after prolonged disease control have not been definitively reported in large series. Records from patients with advanced MSI-H colorectal cancer from The University of Texas - MD Anderson Cancer Center who received immunotherapy between 2014 and 2022 and stopped after prolonged clinical benefit were reviewed. Median progression-free and overall survival were estimated. Associations between the event of recurrence and coexisting mutations (KRAS/NRAS, BRAFV600E), metastatic organ involvement (lung, liver, lymph node, or peritoneum), metastatic timing (synchronous vs. metachronous), prior …

Spatiotemporal Genomic Profiling Of Intestinal Metaplasia Reveals Clonal Dynamics Of Gastric Cancer Progression, Kie Kyon Huang, Haoran Ma, Roxanne Hui Heng Chong, Tomoyuki Uchihara, Benedict Shi Xiang Lian, Feng Zhu, Taotao Sheng, Supriya Srivastava, Su Ting Tay, Raghav Sundar, Angie Lay Keng Tan, Xuewen Ong, Minghui Lee, Shamaine Wei Ting Ho, Tom Lesluyes, Hassan Ashktorab, Duane Smoot, Peter Van Loo, Joy Shijia Chua, Kalpana Ramnarayanan, Louis Ho Shing Lau, Takuji Gotoda, Hyun Soo Kim, Tiing Leong Ang, Christopher Khor, Jonathan Wei Jie Lee, Stephen Kin Kwok Tsao, Wei Lyn Yang, Ming Teh, Hyunsoo Chung, Jimmy Bok Yan So, Khay Guan Yeoh, Patrick Tan, Singapore Gastric Cancer Consortium

Faculty, Staff and Student Publications

Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. Analyzing 1,256 gastric samples (1,152 IMs) across 692 subjects from a prospective 10-year study, we identify 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9). Single-cell and spatial profiles highlight changes in tissue ecology and IM lineage heterogeneity, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling reveals expression-based molecular subtypes of IM associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy …

Metformin: A Potential Treatment For Acne, Hidradenitis Suppurativa And Rosacea, Minah Cho, Yu Ri Woo, Sang Hyun Cho, Jeong Deuk Lee, Hei Sung Kim

Faculty, Staff and Student Publications

Metformin is a widely used drug for treatment of diabetes mellitus, due to its safety and efficacy. In addition to its role as an antidiabetic drug, numerous beneficial effects of metformin have enabled its use in various diseases. Considering the anti-androgenic, anti-angiogenic, anti-fibrotic and antioxidant properties of metformin, it may have the potential to improve chronic inflammatory skin diseases. However, further evidence is needed to confirm the efficacy of metformin in dermatological conditions, This review focuses on exploring the therapeutic targets of metformin in acne vulgaris, hidradenitis suppurativa and rosacea, by studying their pathogeneses.

Allelic Strengths Of Encephalopathy-Associated Uba5 Variants Correlate Between In Vivo And In Vitro Assays, Xueyang Pan, Albert N Alvarez, Mengqi Ma, Shenzhao Lu, Michael W Crawford, Lauren C Briere, Oguz Kanca, Shinya Yamamoto, David A Sweetser, Jenny L Wilson, Ruth J Napier, Jonathan N Pruneda, Hugo J Bellen

Faculty, Staff and Students Publications

Protein UFMylation downstream of the E1 enzyme UBA5 plays essential roles in development and endoplasmic reticulum stress. Variants in the UBA5 gene are associated with developmental and epileptic encephalopathy 44 (DEE44), an autosomal recessive disorder characterized by early-onset encephalopathy, movement abnormalities, global developmental delay, intellectual disability, and seizures. DEE44 is caused by at least 12 different missense variants described as loss of function (LoF), but the relationships between genotypes and molecular or clinical phenotypes remain to be established. We developed a humanized UBA5 fly model and biochemical activity assays in order to describe in vivo and in vitro genotype–phenotype relationships …

Ablation Of Accessory Pathway From Right Atrial Appendage To Anatomic Left Ventricle In L-Transposition Of The Great Arteries, Shree Lata Radhakrishnan, Robert O. Drutel, Cody M. Williams, Raman Danrad, Kelly K. Gajewski, Paul A. Lelorier

School of Medicine Faculty Publications

No abstract provided.

Microstructural Alterations Of Major Thalamic Nuclei In The Chronic Pediatric Spinal Cord Injured Population, K. Kang, K. Fleming, A. Sathe, J. Muller, J. Harrop, D. Middleton, J. Heller, A. Sharan, F. Mohamed, L. Krisa, M. Alizadeh

Department of Radiology Faculty Papers

BACKGROUND: The brain undergoes reorganization following spinal cord injury (SCI), but little is known about how the thalamus is affected in pediatric SCIs.

PURPOSE: To characterize microstructural alterations in the thalamus after SCI with diffusion tensor imaging (DTI) metrics.

METHODS: 18 pediatric participants with chronic SCI (8-20 years) were stratified using the American Spinal Injury Association Impairment Scale (AIS) into groups: A, B, and C/D. DTI of the brain used a 3 T Siemens Verio MRI using the parameters: 20 directions, number of averages = 3, b = 1000 s/mm

DATA ANALYSIS: DTI metrics were acquired by superimposing the AAL3 …

Detection Of Prions In The Urine Of Patients Affected By Sporadic Creutzfeldt-Jakob Disease, M Talke

Faculty, Staff and Student Publications

Objective

Currently, it is unknown whether infectious prions are present in peripheral tissues and biological fluids of patients affected by sporadic Creutzfeldt–Jakob disease (sCJD), the most common prion disorder in humans. This represents a potential risk for inter‐individual prion infection. The main goal of this study was to evaluate the presence of prions in urine of patients suffering from the major subtypes of sCJD.

Methods

Urine samples from sCJD patients spanning the six major subtypes were tested. As controls, we used urine samples from people affected by other neurological or neurodegenerative diseases as well as healthy controls. These samples were …

Decreasing Surgical Complications In Diabetic Patients, Bandana Mahato

DNP Qualifying Manuscripts

Executive Summary

Objective: This manuscript aims to determine if controlling diabetes prior to undergoing low back surgery could decrease complications and disability.

Contexts: Despite the overwhelming information on the complications of uncontrolled diabetes, patients continue to have elevated HgA1C before having surgery. Furthermore, there is a plethora of data showing uncontrolled diabetic patients will have higher complications after surgery, yet patients continue to have elective surgery despite having unchecked diabetes. There are no clear guidelines for primary care providers or surgeons on when they should allow patients to have elective surgery. Therefore, it is vital that HgA1c needs to be …

1756 Evaluating The Impact Of Prophylactic Intrathecal Chemotherapy In Diffuse Large B Cell Lymphoma (Dlbcl) Patients With High Central Nervous System International Prognostic Index (Cns-Ipi) Scores: A Comprehensive Review And Meta-Analysis, Kadhim Al-Banaa, Alfarooq Alshaikhli, Shyam Poudel, Shiva Shrotria, Can Wang, Paul Hanona, Swathi Gopishetty, Precious Idogun, Daniel Ezekwudo, Ishmael Jaiyesimi

Conference Presentation Abstracts

No abstract provided.

Diet And Nutrition In Inflammatory Bowel Disease: A Review Of The Literature, Scott Manski, Nicholas Noverati, Tatiana Policarpo, Emily Rubin, Raina Shivashankar

Division of Gastroenterology and Hepatology Faculty Papers

Diet is thought to contribute to the development of inflammatory bowel disease (IBD) and may act as a mediator of inflammation in patients with IBD. Patients commonly associate their diet with symptoms and inquire about dietary modifications to manage their IBD. Without clinical guidelines and well-established nutritional data, healthcare providers managing patients with IBD may find it difficult to provide recommendations. Strong evidence for enteral nutrition, particularly in the pediatric population, has been established in Crohn's disease (CD) as a therapeutic option. Enteral nutrition may also serve as an adjunct to an exclusion diet. Recent studies such as the randomized …

The Dna Glycosylase Neil2 Is Protective During Sars-Cov-2 Infection, Nisha Tapryal, Anirban Chakraborty, Kaushik Saha, Azharul Islam, Lang Pan, Koa Hosoki, Ibrahim M Sayed, Jason M Duran, Joshua Alcantara, Vanessa Castillo, Courtney Tindle, Altaf H Sarker, Maki Wakamiya, Victor J Cardenas, Gulshan Sharma, Laura E Crotty Alexander, Sanjiv Sur, Debashis Sahoo, Gourisankar Ghosh, Soumita Das, Pradipta Ghosh, Istvan Boldogh, Tapas K Hazra

Faculty, Staff and Students Publications

SARS-CoV-2 infection-induced aggravation of host innate immune response not only causes tissue damage and multiorgan failure in COVID-19 patients but also induces host genome damage and activates DNA damage response pathways. To test whether the compromised DNA repair capacity of individuals modulates the severity of COVID-19 infection, we analyze DNA repair gene expression in publicly available patient datasets and observe a lower level of the DNA glycosylase NEIL2 in the lungs of severely infected COVID-19 patients. This observation of lower NEIL2 levels is further validated in infected patients, hamsters and ACE2 receptor-expressing human A549 (A549-ACE2) cells. Furthermore, delivery of recombinant …

Sirtuin 6 Activation Rescues The Age-Related Decline In Dna Damage Repair In Primary Human Chondrocytes, Michaela E. Copp, Jacqueline Shine, Hannon L. Brown, Kirti R. Nimmala, Oliver B. Hansen, Susan Chubinskaya, John A. Collins, Richard F. Loeser, Brian O. Diekman

Department of Orthopaedic Surgery Faculty Papers

While advanced age is widely recognized as the greatest risk factor for osteoarthritis (OA), the biological mechanisms behind this connection remain unclear. Previous work has demonstrated that chondrocytes from older cadaveric donors have elevated levels of DNA damage as compared to chondrocytes from younger donors. The purpose of this study was to determine whether a decline in DNA repair efficiency is one explanation for the accumulation of DNA damage with age, and to quantify the improvement in repair with activation of Sirtuin 6 (SIRT6). After acute damage with irradiation, DNA repair was shown to be more efficient in chondrocytes from …

Fully-Automated, Ct-Only Gtv Contouring For Palliative Head And Neck Radiotherapy, Skylar S Gay, Carlos E Cardenas, Callistus Nguyen, Tucker J Netherton, Cenji Yu, Yao Zhao, Stephen Skett, Tina Patel, Delali Adjogatse, Teresa Guerrero Urbano, Komeela Naidoo, Beth M Beadle, Jinzhong Yang, Ajay Aggarwal, Laurence E Court

Faculty, Staff and Student Publications

Planning for palliative radiotherapy is performed without the advantage of MR or PET imaging in many clinics. Here, we investigated CT-only GTV delineation for palliative treatment of head and neck cancer. Two multi-institutional datasets of palliative-intent treatment plans were retrospectively acquired: a set of 102 non-contrast-enhanced CTs and a set of 96 contrast-enhanced CTs. The nnU-Net auto-segmentation network was chosen for its strength in medical image segmentation, and five approaches separately trained: (1) heuristic-cropped, non-contrast images with a single GTV channel, (2) cropping around a manually-placed point in the tumor center for non-contrast images with a single GTV channel, (3) …

Capacity Assessment And Spatial Analysis Of Cervical Cancer Services In The Gambia, Meghan E Mali, Ousman Sanyang, Katherine L Harris, Justin Sorensen, Mustapha Bittaye, Jonathan Nellermoe, Raymond R Price, Edward K Sutherland

Faculty, Staff and Student Publications

Background

Cervical cancer is the most common cancer and the leading cause of cancer-related death in Gambian women. The Gambian Ministry of Health is striving to improve access to screening, diagnostic, and treatment services for cervical cancer, but comprehensive data on currently available services is limited making it challenging to appropriately prioritize the ideal next steps for expanding care. This study aims to describe the current services available for the prevention, screening, and treatment of cervical cancer in The Gambia and provide suggestions for expanding geographic access to care.

Methods

A survey aimed at assessing the availability of key cervical …

C-Case 2023: Promoting Excellence In Surgical Education: Canadian Conference For The Advancement Of Surgical Education, Oct. 12-13, 2023, Montréal, Quebec, Jeffrey Sioufi, Brandon Hall, Ryan Antel, Sarah Moussa, Mathushan Subasri, Mustafa Fakih, Nehal Islam, Reggie C. Hamdy, Sonaina Chopra, Karim Damji

Department of Ophthalmology & Visual Sciences

No abstract provided.

Preoperative Computed Tomography Scan In Distal Radius Fractures And The Effect On Preoperative Planning, Adam L. Haydel, Ryan C. Roubion, Cristina T. Graphia, Corinne E. Cloud, Claudia Leonardi, Christopher E. Marrero

School of Medicine Faculty Publications

Purpose: It is unclear whether computed tomography (CT) scans alter the surgical plan when ordered before surgery for fixation of intra-articular distal radius fractures (DRFs). The purpose of this study was to determine whether a preoperative CT scan alters the planned approach (PA) or planned fixation strategy (PFS) for open reduction internal fixation of intra-articular DRFs. Methods: Radiology records were retrospectively reviewed by one trauma surgeon and two hand surgeons for 33 intra-articular DRFs that met the inclusion criteria and previously underwent open reduction internal fixation. Surgeons were initially provided only preoperative radiographs; they were asked for their PA and …

Exosome Shedding Is Concordant With Objective Treatment Response Rate And Stratifies Time To Progression In Treatment Naïve, Non-Resectable Hepatocellular Carcinoma, Kelley G. Núñez, Dorota Wyczechowska, Mina Hibino, Tyler Sandow, Juan Gimenez, Ali R. Koksal, Yucel Aydin, Srikanta Dash, Ari J. Cohen, Paul T. Thevenot

School of Medicine Faculty Publications

Translational strategies to characterize and monitor extracellular vesicles such as exosome (EX) shedding and the clinical impact of this data within hepatocellular carcinoma (HCC) remains unclear. In this study, EX shedding was assessed in early-stage HCC and evaluated as a stratification factor for time to progression (TTP) following first-cycle liver-directed therapy (LDT). Plasma EXs were isolated from HCC patients undergoing LDT using ultracentrifugation. Purified EXs were stained using markers CD9 and CD63 and quantified using an ImageStreamX flow cytometer. Circulating EXs expressing CD9 were isolated at 10-fold higher levels compared to CD63. The intensity of CD9+ EX shedding following LDT …

Aged And Induced-Premature Ovarian Failure Mouse Models Affect Diestrus Profile And Ovarian Features, Ana Carolina Zucon Bacelar, Nataira Regina Momesso, Felipe Haddad Martim Pederro, Alaíde Gonçalves, Edilson Ervolino, Antonio Hernandes Chaves-Neto, Cláudia Cristina Biguetti, Mariza Akemi Matsumoto

School of Podiatric Medicine Publications

Sex hormones exert a wide influence on several systems of the human body, especially in women, who undergo intense changes in the trans and postmenopausal periods. Different experimental models are used to mimic these conditions; however, the impact on hormonal profile may be different. This study aimed to analyze and compare vaginal cytology of different post-estropausal mice models, along with their microscopical ovarian features. Forty-six C57BL/6J female mice with the ages of 4, 6 and 18 months at the beginning of the experiment, weighing about 25–28 grams, constituted five groups: NC–(negative control) animals with no treatment, OVX-SHAM—sham ovariectomized, OVX–ovariectomized, VCD–medicated …

Improving Access To Early Interventions For Prediabetic Patients, Kimberleigh M. Telling

Doctor of Nursing Practice Projects

Approximately 88 million Americans, or nearly one-third of the population, have prediabetes. This condition has a high rate of progression to type 2 diabetes, reaching 70%. However, early identification, diagnosis, and participation in lifestyle interventions can effectively reduce the risk and promote euglycemia. Regrettably, 85% of those with prediabetes are unaware. The goal of this quantitative quality improvement project was to enhance the use of the prediabetes diagnosis code by primary care providers, who play a crucial role in preventing type 2 diabetes. The purpose was to improve access to early intervention for individuals with prediabetes, following the guidelines of …

Evaluating Clinical Outcomes In Patients Being Treated Exclusively Via Telepsychiatry: Retrospective Data Analysis, Cheryl Person, Nicola O'Connor, Lucy Koehler, Kartik Venkatachalam, Georgia Gaveras

Faculty, Staff and Student Publications

BACKGROUND: Depression and anxiety are highly prevalent conditions in the United States. Despite the availability of suitable therapeutic options, limited access to high-quality psychiatrists represents a major barrier to treatment. Although telepsychiatry has the potential to improve access to psychiatrists, treatment efficacy in the telepsychiatry model remains unclear.

OBJECTIVE: Our primary objective was to determine whether there was a clinically meaningful change in 1 of 2 validated outcome measures of depression and anxiety-the Patient Health Questionnaire-8 (PHQ-8) or the Generalized Anxiety Disorder-7 (GAD-7)-after receiving at least 8 weeks of treatment in an outpatient telepsychiatry setting.

METHODS: We included treatment-seeking patients …

Therapeutic Effect Of Echinococcus Granulosus Cyst Fluid On Bacterial Sepsis In Mice, Shuying Wang, Donghui Jiang, Feifei Huang, Yayun Qian, Meitao Qi, Huihui Li, Xiaoli Wang, Zhi Wang, Kaigui Wang, Yin Wang, Pengfei Du, Bin Zhan, Rui Zhou, Liang Chu, Xiaodi Yang

Faculty, Staff and Students Publications

BACKGROUND: The primary pathophysiological process of sepsis is to stimulate a massive release of inflammatory mediators to trigger systemic inflammatory response syndrome (SIRS), the major cause of multi-organ dysfunction and death. Like other helminths, Echinococcus granulosus induces host immunomodulation. We sought to determine whether E. granulosus cyst fluid (EgCF) displays a therapeutic effect on sepsis-induced inflammation and tissue damage in a mouse model.

METHODS: The anti-inflammatory effects of EgCF were determined by in vitro culture with bone marrow-derived macrophages (BMDMs) and in vivo treatment of BALB/C mice with cecal ligation and puncture (CLP)-induced sepsis. The macrophage phenotypes were determined by …

Nicotinic Acetylcholine Receptor Signaling Maintains Epithelial Barrier Integrity, Nadja S Katheder, Kristen C Browder, Diana Chang, Ann De Maziere, Pekka Kujala, Suzanne Van Dijk, Judith Klumperman, Tzu-Chiao Lu, Hongjie Li, Zijuan Lai, Dewakar Sangaraju, Heinrich Jasper

Faculty, Staff and Students Publications

Disruption of epithelial barriers is a common disease manifestation in chronic degenerative diseases of the airways, lung, and intestine. Extensive human genetic studies have identified risk loci in such diseases, including in chronic obstructive pulmonary disease (COPD) and inflammatory bowel diseases. The genes associated with these loci have not fully been determined, and functional characterization of such genes requires extensive studies in model organisms. Here, we report the results of a screen in

Identification Of Ct-Based Non-Invasive Radiomic Biomarkers For Overall Survival Prediction In Oral Cavity Squamous Cell Carcinoma, Xiao Ling, Gregory S. Alexander, Jason Molitoris, Jinhyuk Choi, Lisa Schumaker, Ranee Mehra, Daria A. Gaykalova, Lei Ren

Department of Radiation Oncology Faculty Papers

This study addresses the limited non-invasive tools for Oral Cavity Squamous Cell Carcinoma (OSCC) survival prediction by identifying Computed Tomography (CT)-based biomarkers to improve prognosis prediction. A retrospective analysis was conducted on data from 149 OSCC patients, including CT radiomics and clinical information. An ensemble approach involving correlation analysis, score screening, and the Sparse-L1 algorithm was used to select functional features, which were then used to build Cox Proportional Hazards models (CPH). Our CPH achieved a 0.70 concordance index in testing. The model identified two CT-based radiomics features, Gradient-Neighboring-Gray-Tone-Difference-Matrix-Strength (GNS) and normalized-Wavelet-LLL-Gray-Level-Dependence-Matrix-Large-Dependence-High-Gray-Level-Emphasis (HLE), as well as stage and alcohol usage, …

Effects Of Independent Versus Dependent Stressful Life Events On Major Symptom Domains Of Schizophrenia, Yizhou Ma, Joshua Chiappelli, Mark D Kvarta, Heather Bruce, Andrew Van Der Vaart, Eric L Goldwaser, Xiaoming Du, Hemalatha Sampath, Samantha Lightner, Jane Endres, Akram Yusuf, Alexa Yuen, Samantha Narvaez, Danny Campos-Saravia, Peter Kochunov, L Elliot Hong

Faculty, Staff and Student Publications

We evaluated two models to link stressful life events (SLEs) with the psychopathology of schizophrenia spectrum disorders (SSD). We separated SLEs into independent (iSLEs, unlikely influenced by one's behavior) and dependent (dSLEs, likely influenced by one's behavior). Stress-diathesis and stress generation models were evaluated for the relationship between total, i- and d- SLEs and the severity of positive, negative, and depressive symptoms in participants with SSD. Participants with SSD (n = 286; 196 males; age = 37.5 ± 13.5 years) and community controls (n = 121; 83 males; 35.4 ± 13.9 years) completed self-report of lifetime negative total, i- and …

Ewsr1::Atf1 Orchestrates The Clear Cell Sarcoma Transcriptome In Human Tumors And A Mouse Genetic Model, Benjamin B Ozenberger, Li Li, Emily R Wilson, Alexander J Lazar, Jared J Barrott, Kevin B Jones

Faculty, Staff and Student Publications

Clear cell sarcoma (CCS) is a rare, aggressive malignancy that most frequently arises in the soft tissues of the extremities. It is defined and driven by expression of one member of a family of related translocation-generated fusion oncogenes, the most common of which is EWSR1::ATF1. The EWSR1::ATF1 fusion oncoprotein reprograms transcription. However, the binding distribution of EWSR1::ATF1 across the genome and its target genes remain unclear. Here, we interrogated the genomic distribution of V5-tagged EWSR1::ATF1 in tumors it had induced upon expression in mice that also recapitulated the transcriptome of human CCS. ChIP-sequencing of V5-EWSR1::ATF1 identified previously unreported motifs …

Optical Genome Mapping Helps To Identify Bcr::Jak2 Rearrangement Arising From Cryptic Complex Chromosomal Aberrations: A Case Report And Literature Review, Neelam Vanjari, Guilin Tang, Gokce A Toruner, Wei Wang, Beenu Thakral, Ming Zhao, Bhavana J Dave, Joseph D Khoury, L Jeffrey Medeiros, Zhenya Tang

Faculty, Staff and Student Publications

We report a case of myeloproliferative neoplasm, not otherwise specified (MPN-NOS)-transformed AML with BCR::JAK2 rearrangement. Chromosomal analysis indicated a simple abnormal karyotype 46,XY,t(7;17)(q21;q24),t(9;22)(p24;q11.2). Fluorescence in situ hybridization (FISH) using a BCR/ABL1/ASS1 probe set suggested a possible BCR rearrangement and a reflex JAK2 breakapart probe indicated JAK2 rearrangement, most likely partnered with BCR. Optical genome mapping (OGM) analysis confirmed BCR::JAK2 derived through an inv(9)(p24p13) after a t(9;22)(p13;q11.2) in this case. Due to the complexity of chromosomal aberrations, disruption and/or rearrangement of other genes such as KIF24::BCR, JAK2::KIF24/UBAP1, and CDK6:SOX9 were also identified by OGM. Although the functionality and clinical …

Novel Sox10 Indel Mutations Drive Schwannomas Through Impaired Transactivation Of Myelination Gene Programs, Erik A Williams, Ajay Ravindranathan, Rohit Gupta, Nicholas O Stevers, Abigail K Suwala, Chibo Hong, Somang Kim, Jimmy Bo Yuan, Jasper Wu, Jairo Barreto, Calixto-Hope G Lucas, Emily Chan, Melike Pekmezci, Philip E Leboit, Thaddeus Mully, Arie Perry, Andrew Bollen, Jessica Van Ziffle, W Patrick Devine, Alyssa T Reddy, Nalin Gupta, Kristen M Basnet, Robert J B Macaulay, Patrick Malafronte, Han Lee, William H Yong, Kevin Jon Williams, Tareq A Juratli, Douglas A Mata, Richard S P Huang, Matthew C Hiemenz, Dean C Pavlick, Garrett M Frampton, Tyler Janovitz, Jeffrey S Ross, Susan M Chang, Mitchel S Berger, Line Jacques, Jun S Song, Joseph F Costello, David A Solomon

Faculty, Staff and Student Publications

BACKGROUND: Schwannomas are common peripheral nerve sheath tumors that can cause severe morbidity given their stereotypic intracranial and paraspinal locations. Similar to many solid tumors, schwannomas and other nerve sheath tumors are primarily thought to arise due to aberrant hyperactivation of the RAS growth factor signaling pathway. Here, we sought to further define the molecular pathogenesis of schwannomas.

METHODS: We performed comprehensive genomic profiling on a cohort of 96 human schwannomas, as well as DNA methylation profiling on a subset. Functional studies including RNA sequencing, chromatin immunoprecipitation-DNA sequencing, electrophoretic mobility shift assay, and luciferase reporter assays were performed in a …