Digital Commons Network^™

Prediction Of Brain Metastases Development In Patients With Lung Cancer By Explainable Artificial Intelligence From Electronic Health Records, Zhao Li, Rongbin Li, Yujia Zhou, Laila Rasmy, Degui Zhi, Ping Zhu, Antonio Dono, Xiaoqian Jiang, Hua Xu, Yoshua Esquenazi, W Jim Zheng

Faculty, Staff and Student Publications

PURPOSE: Early detection of brain metastases (BMs) is critical for prompt treatment and optimal control of the disease. In this study, we seek to predict the risk of developing BM among patients diagnosed with lung cancer on the basis of electronic health record (EHR) data and to understand what factors are important for the model to predict BM development through explainable artificial intelligence approaches accurately.

MATERIALS AND METHODS: We trained a recurrent neural network model, REverse Time AttentIoN (RETAIN), to predict the risk of developing BM using structured EHR data. To interpret the model's decision process, we analyzed the attention …

Effects Of Diet On Lcn2 Expression And Onset Of Neuroinflammation In An Alzheimer’S Disease Mice Model, Abdirahman A. Hayir

Neuroscience Honors Projects

This project covers the findings regarding the impact of diet on lipocalin 2 (LCN2) and the effects it has on neuroinflammation Alzheimer’s Disease (AD). LCN2 is a protein that is critical to the functionality of mitochondria and inflammatory responses. Evidence has shown that mitochondrial dysfunction is a potential central event in driving AD pathogenesis and contributing to formation of pathological hallmarks such as chronic inflammation. Furthermore, studies have shown that LCN2 can be deficient under metabolic conditions such as high-fat-diet (HFD). This study investigates if HFD induces LCN2 deficiency and increased neuroinflammation in an AD mice model.

Measuring Claim-Evidence-Reasoning Using Scenario-Based Assessments Grounded In Real-World Issues, William L. Romine, Amy Lannin, Ankita Agarwal, Maha Kareem, Emily Burwell

Biological Sciences Faculty Publications

Improving students’ use of argumentation is front and center in the increasing emphasis on scientific practice in K-12 Science and STEM programs. We explore the construct validity of scenario-based assessments of claim-evidence-reasoning (CER) and the structure of the CER construct with respect to a learning progression framework. We also seek to understand how middle school students progress. Establishing the purpose of an argument is a competency that a majority of middle school students meet, whereas quantitative reasoning is the most difficult, and the Rasch model indicates that the competencies form a unidimensional hierarchy of skills. We also find no evidence …

Oral Health In Relation To The Covid-19 Pandemic, Anika L. Gram

Honors Thesis

Oral health has seen significant changes through the Covid-19 pandemic. Many people experienced the lifestyle alteration of wearing a mask for a major portion of their day-to-day life, and some went to the dentist significantly less than they did pre-pandemic. The literature review explores dental practices during the Covid-19 pandemic. It also examines mask-wearing behaviors both before and during the pandemic and the research that has been conducted previously regarding the potential effects of mask-wearing. Despite the decrease in use of masks post-pandemic, many healthcare professionals continue to wear masks daily. Additionally, in the event of future disease outbreak, it …

Jurisgenerative Tissues: Sociotechnical Imaginaries And The Legal Secretions Of 3d Bioprinting, Roxanne Mykitiuk, Joshua Shaw

Articles & Book Chapters

Three-dimensional ‘bioprinting’ is under development, which may produce living human organs and tissues to be surgically implanted in patients. Like tissue engineering and regenerative medicine generally, the process of bioprinting potentially disrupts experience of the human body by redefining understandings of, and becoming actualised in new practices and regimes in relation to, the body. The authors consider how these novel sociotechnical imaginaries may emerge, having regard to law’s contribution to, as well as its possible transformation by, the process of 3D bioprinting. The authors draw on Gilbert Simondon and corporeal, material feminists to account for these disruptions as ‘ontogenetic,’ in …

Regeneration Of Neurons In Human Brain Tissue; A Revolutionary Concept With Therapeutic Potential, Mackenzie R. Dunn

Biomedical Sciences Undergraduate Research

There is current research to suggest that endogenous neuronal regeneration, exogenous neuronal stem cell transplantation and glial cell reprogramming could be prospective therapeutic treatments for neurodegeneration and traumatic injury. With these conditions, there is significant brain atrophy, loss of neurons and loss of synaptic connections which can have devastating effects on executive functioning, cognition, learning and memory. This review will examine these modern approaches to adult neurogenesis, and assess the viable mechanisms and future outlook of these three therapies for neurological regenerative medicine.

The Effects Of Exercise On The Lipid Profile Of Extracellular Vesicles, Tesha Kerr

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

We sought to ascertain the effect of different types of exercise (aerobic training and resistance training) on the lipid profile of extracellular vesicles. Thus, we had participants perform bouts of AT and RT and rest (control) and collected blood samples from them immediately after (timepoint 0) and 30 minutes after (timepoint 30) exercise. Small extracellular vesicles (sEVs) were isolated from plasma of participants using cushioned-density gradient ultracentrifugation (C-DGUC). Small EV size, morphology, and protein markers were determined using nanoparticle tracking analysis, transmission electron microscopy, and western blot, respectively. Additionally, we performed untargeted lipidomics on the sEV isolate. We found that …

The Revolutionary Genome Editor: Crispr-Cas9 Systems, Grace Spade

Senior Honors Theses

Genetic engineering is the modification of an organism's genetic material to alter its traits through adding, deleting, or changing specific genes. CRISPR-Cas9 systems are groundbreaking tools for genetic engineering, in short utilizing a molecule called RNA to guide a protein called Cas9 to a specific location in DNA to add, delete, or replace genes. The history of how the CRISPR-Cas9 systems came into existence, how it was adapted from a natural defense system in bacteria, and its mechanism of action in both are explained. Its applications, both present and future, competing genetic modifiers, advantages and disadvantages, and the ethical dilemmas …

In Vitro Gametogenesis: A Research Timeline And Implications For The Future Of Assisted Reproductive Technology, Nicole Buckley

Senior Honors Theses

The novel reproductive technology, In Vitro Gametogenesis (IVG), includes the process of obtaining mature viable germ cells from pluripotent stem cells. To do so, embryonic stem cells and induced pluripotent stem cells are specified to primordial germ cells and differentiated to form gametes that undergo further maturation, which subsequently may undergo in vitro fertilization to form an embryo. With this capability, IVG holds the power to provide a novel treatment option for human infertility. As of now, research has been conducted on mice successfully, and with limited success in humans. Future research will likely focus on discovering the species-specific differences …

Investigating The Effects Of Sex And Carvedilol On Ischemia Preconditioning Protective Effect, Casey Jc Miller

Honors Thesis

Many studies have been done on ischemic preconditioning and its protective effects using the murine model with overwhelmingly consistent and promising results. However, many clinical trials have failed to demonstrate the protective effects of ischemic preconditioning. The causes of the inconsistency are unknown. The effect of sex on ischemic preconditioning protection is largely unclear, which may be a contributing factor. Additionally, in clinical trials, the recruited patients were most likely taking some medications. This project aimed to test the differences in sex on preconditioning protection and the effect of a common β-blocker medication, Carvedilol, on preconditioning protection. Tourniquet-induced unilateral hindlimb …

The Non-Coding Rna Journal Club: Highlights On Recent Papers—12, Patrick K.T. Shiu, Mirolyuba Ilieva, Anja Holm, Shizuka Uchida, Johanna K. Distefano, Agnieszka Bronisz, Ling Yang, Yoh Asahi, Ajay Goel, Liuqing Yang, Ashok Nuthanakanti, Alexander Serganov, Suresh K. Alahari, Chunru Lin, Barbara Pardini, Alessio Naccarati, Jing Jin, Beshoy Armanios, Xiao Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, André P. Gerber, He Lin, Simon J. Conn, Doha Magdy Mostafa Sleem

School of Graduate Studies Faculty Publications

No abstract provided.

2023 Research Day Program, Lincoln Memorial University

Research Day

This program contains abstracts and presentation summaries from LMU's 2023 Annual Research Day conference.

Health Consequences Of Low Energy Availability In Females And Their Underlying Physiological Mechanisms, Grace Parry

Senior Honors Theses

Low energy availability (LEA) is a state in which energy intake is insufficient to support energy expenditure while maintaining energy balance, which has been shown to result in gastrointestinal distress, immunosuppression, reduced metabolic rate, menstrual dysfunction, diminished bone health, and impaired cardiovascular function in females. Alterations to the microbiome and mucosal lining may propagate gastrointestinal complaints and compromised immune function associated with LEA. The pathophysiology of LEA is otherwise largely driven by hormonal adaptations. Diminished production of thyroid hormones is known to contribute to reduced metabolic rate. Decreases in leptin and insulin and increases in ghrelin disrupt reproductive function through …

Dean's Report- Spring 2023, Marina K. Holz

GSBMS Dean’s Report

No abstract provided.

Somatostatin Regulates Central Clock Function And Circadian Responses To Light, Deborah A.M. Joye, Kayla E. Rohr, Kimberlee Suenkens, Alissa Wuorinen, Thomas Inda, Madeline Arzbecker, Emma Mueller, Alec Huber, Harshida Pancholi, Murray G. Blackmore, Vania Carmona-Alcocer, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Daily and annual changes in light are processed by central clock circuits that control the timing of behavior and physiology. The suprachiasmatic nucleus (SCN) in the anterior hypothalamus processes daily photic inputs and encodes changes in day length (i.e., photoperiod), but the SCN circuits that regulate circadian and photoperiodic responses to light remain unclear. Somatostatin (SST) expression in the hypothalamus is modulated by photoperiod, but the role of SST in SCN responses to light has not been examined. Our results indicate that SST signaling regulates daily rhythms in behavior and SCN function in a manner influenced by sex. First, we …

Investigation Of Clinically Relevant Fluconazole Resistance Mechanisms In The Fungal Pathogen Candida Parapsilosis, Laura Anne Doorley

Theses and Dissertations (ETD)

Invasive candidiasis is a severe fungal infection associated with significant morbidity and mortality, particularly among the critically ill and immunocompromised. Candida parapsilosis is the most common non-albicans species causing invasive Candida infections in pediatric and neonatal populations worldwide and is particularly common in the countries of South America, Western Asia, Mediterranean Europe, and Southern Africa. For many of these countries, fluconazole and other triazoles are the first line antifungal agents used for effective treatment of invasive Candida infection. Until recently, rates of fluconazole resistance among C. parapsilosis isolates were relatively low, therefore the determination of clinically relevant resistance mechanisms in …

Leukocyte Tyrosine Kinase (Ltk) Is The Mendelian Determinant Of The Axolotl Melanoid Color Variant, Mirindi Kabangu, Raissa Cecil, Lloyd Strohl Ii, Nataliya Y. Timoshevskaya, Jeramiah James Smith, Stephen Randal Voss

Markey Cancer Center Faculty Publications

The great diversity of color patterns observed among amphibians is largely explained by the differentiation of relatively few pigment cell types during development. Mexican axolotls present a variety of color phenotypes that span the continuum from leucistic to highly melanistic. The melanoid axolotl is a Mendelian variant characterized by large numbers of melanophores, proportionally fewer xanthophores, and no iridophores. Early studies of melanoid were influential in developing the single-origin hypothesis of pigment cell development, wherein it has been proposed that all three pigment cell types derive from a common progenitor cell, with pigment metabolites playing potential roles in directing the …

A Design, Development, And Evaluation Of Bio-Patch For Myocardial Tissue Repair, Yaya Zhang

Theses and Dissertations (ETD)

Introduction. Ischemic heart disease (IHD) is a major concern of human health issue. The structural repair and functional recovery of injured hearts is a major challenge in the clinical setting. Preclinical studies over last 10 years have demonstrated the potential of using stem cells to treat IHD, but the efficacy of this therapy is jeopardized by uncontrollable migration and low survival of the injected stem cells. An approach based on tissue engineering enabling target-specific stem cell delivery such as cardiac patches has emerged as an alternative solution for stem cell therapy for IHD. It employs scaffold materials to engulf various …

Modulation Of Cerebral Artery Smooth Muscle Bk Channel Function By Neurosteroids, Kelsey Caroline Cleland North

Theses and Dissertations (ETD)

Voltage-gated and Ca2+ activated K+ channels of large conductance (BK) channels are essential for many key physiological processes, such as controlling the contraction of smooth muscle, including cerebrovascular smooth muscle. Importantly, BK channels are made up of a homotetramer of α subunits which associate with accessory β subunits. These β subunits alter the activity of the channel; this modulation is subunit-specific. Moreover, these accessory subunits have tissue-specific expression, such that the β1 subunit is highly expressed within cerebrovascular smooth muscle and greatly increases the open probability of BK channels. Increased BK channel open probability is linked to increased dilation of …

Vascular Mechanisms Of Rhabdomyolysis-Induced Acute Kidney Injury, Jeremiah Moyinolu Afolabi

Theses and Dissertations (ETD)

In patients with rhabdomyolysis, the overwhelming release of myoglobin into circulation is the primary cause of kidney injury. Myoglobin causes direct kidney injury as well as severe renal vasoconstriction. An increase in renal vascular resistance (RVR) results in renal blood flow (RBF) and glomerular filtration rate (GFR) reduction, tubular injury, and acute kidney injury (AKI). The mechanisms that underlie rhabdomyolysis-induced AKI are not fully understood but may involve the local production of vasoactive mediators in the kidney. Myoglobin stimulated endothelin-1 (ET-1) production in proximal tubular cells, an effect driven by NADPH oxidase-dependent oxyradical generation. Rats subjected to glycerol-induced rhabdomyolysis also …

Quantification Of The Role Of Lead Foil In Flattening Filter Free Beam Reference Dosimetry, Song Gao, Christopher Nelson, Congjun Wang, Vindu Kathriarachchi, Michael Choi, Rishik Saxena, Robin Kendall, Peter Balter

Faculty, Staff and Student Publications

PURPOSE: To quantify the potential error in outputs for flattening filter free (FFF) beams associated with use of a lead foil in beam quality determination per the addendum protocol for TG-51, we examined differences in measurements of the beam quality conversion factor k

METHODS: Two FFF beams, a 6 MV FFF and a 10 MV FFF, were calibrated on eight Varian TrueBeams and two Elekta Versa HD linear accelerators (linacs) according to the TG-51 addendum protocol by using Farmer ionization chambers [TN 30013 (PTW) and SNC600c (Sun Nuclear)] with traceable absorbed dose-to-water calibrations. In determining k

RESULTS: Differences in %dd(10)x …

Inconsistent Partitioning And Unproductive Feature Associations Yield Idealized Radiomic Models, Mishka Gidwani, Ken Chang, Jay Biren Patel, Katharina Viktoria Hoebel, Syed Rakin Ahmed, Praveer Singh, Clifton David Fuller, Jayashree Kalpathy-Cramer

Faculty, Staff and Student Publications

Background Radiomics is the extraction of predefined mathematic features from medical images for the prediction of variables of clinical interest. While some studies report superlative accuracy of radiomic machine learning (ML) models, the published methodology is often incomplete, and the results are rarely validated in external testing data sets. Purpose To characterize the type, prevalence, and statistical impact of methodologic errors present in radiomic ML studies. Materials and Methods Radiomic ML publications were reviewed for the presence of performance-inflating methodologic flaws. Common flaws were subsequently reproduced with randomly generated features interpolated from publicly available radiomic data sets to demonstrate the …

Advancing Car T Cell Therapy Through The Use Of Multidimensional Omics Data, Jingwen Yang, Yamei Chen, Ying Jing, Michael R Green, Leng Han

Faculty, Staff and Student Publications

Despite the notable success of chimeric antigen receptor (CAR) T cell therapies in the treatment of certain haematological malignancies, challenges remain in optimizing CAR designs and cell products, improving response rates, extending the durability of remissions, reducing toxicity and broadening the utility of this therapeutic modality to other cancer types. Data from multidimensional omics analyses, including genomics, epigenomics, transcriptomics, T cell receptor-repertoire profiling, proteomics, metabolomics and/or microbiomics, provide unique opportunities to dissect the complex and dynamic multifactorial phenotypes, processes and responses of CAR T cells as well as to discover novel tumour targets and pathways of resistance. In this Review, …

Fear Of Recurrence, Emotional Well-Being And Quality Of Life Among Long-Term Advanced Ovarian Cancer Survivors, Kathryn Osann, Lari Wenzel, Chelsea Mckinney, Lynne Wagner, David Cella, Giulia Fulci, Mary J Scroggins, Heather A Lankes, Victoria Wang, Kenneth P Nephew, George L Maxwell, Samuel C Mok, Thomas P Conrads, Austin Miller, Michael Birrer

Faculty, Staff and Student Publications

OBJECTIVE: Although advanced stage epithelial ovarian cancer is widely considered life-threatening, 17% of women with advanced disease will survive long-term. Little is known about the health-related quality of life (QOL) of long-term ovarian cancer survivors, or how fear of recurrence might affect QOL.

METHODS: 58 long-term survivors with advanced disease participated in the study. Participants completed standardized questionnaires to capture cancer history, QOL, and fear of recurrent disease (FOR). Statistical analyses included multivariable linear models.

RESULTS: Participants averaged 52.8 years at diagnosis and had survived >8 years (mean:13.5); 64% had recurrent disease. Mean FACT-G, FACT-O, and FACT-O-TOI (TOI) scores were …

The Glycoprotein Cd147 Defines Mirna-Enriched Extracellular Vesicles That Derive From Cancer Cells, Song Yi Ko, Wonjae Lee, Melanie Weigert, Eric Jonasch, Ernst Lengyel, Honami Naora

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) are ideal for liquid biopsy, but distinguishing cancer cell‐derived EVs and subpopulations of biomarker‐containing EVs in body fluids has been challenging. Here, we identified that the glycoproteins CD147 and CD98 define subpopulations of EVs that are distinct from classical tetraspanin+ EVs in their biogenesis. Notably, we identified that CD147+ EVs have substantially higher microRNA (miRNA) content than tetraspanin+ EVs and are selectively enriched in miRNA through the interaction of CD147 with heterogeneous nuclear ribonucleoprotein A2/B1. Studies using mouse xenograft models showed that CD147+ EVs predominantly derive from cancer cells, whereas the majority of tetraspanin+ EVs are not …

Emerging Role Of Tak1 In The Regulation Of Skeletal Muscle Mass, Anirban Roy, Vihang A Narkar, Ashok Kumar

Faculty, Staff and Student Publications

Maintenance of skeletal muscle mass and strength throughout life is crucial for heathy living and longevity. Several signaling pathways have been implicated in the regulation of skeletal muscle mass in adults. TGF-β-activated kinase 1 (TAK1) is a key protein, which coordinates the activation of multiple signaling pathways. Recently, it was discovered that TAK1 is essential for the maintenance of skeletal muscle mass and myofiber hypertrophy following mechanical overload. Forced activation of TAK1 in skeletal muscle causes hypertrophy and attenuates denervation-induced muscle atrophy. TAK1-mediated signaling in skeletal muscle promotes protein synthesis, redox homeostasis, mitochondrial health, and integrity of neuromuscular junctions. In …

Hyperphosphorylated Tau In Mesial Temporal Lobe Epilepsy: A Neuropathological And Cognitive Study, Eliana C B Toscano, Érica L M Vieira, Lea T Grinberg, Natalia P Rocha, Joseane A S Brant, Regina S Paradela, Alexandre V Giannetti, Claudia K Suemoto, Renata E P Leite, Ricardo Nitrini, Milene A Rachid, Antonio L Teixeira

Faculty, Staff and Student Publications

Temporal lobe epilepsy (TLE) often courses with cognitive deficits, but its underlying neuronal basis remains unclear. Confluent data suggest that epilepsy share pathophysiological mechanisms with neurodegenerative diseases. However, as most studies analyze subjects 60 years old and older, it is challenging to rule out that neurodegenerative changes arise from age-related mechanisms rather than epilepsy in these individuals. To fill this gap, we conducted a neuropathological investigation of the hippocampal formation of 22 adults with mesial TLE and 20 age- and sex-matched controls (both younger than 60 years). Moreover, we interrogated the relationship between these neuropathological metrics and cognitive performance. Hippocampal …

Genomic-Transcriptomic Evolution In Lung Cancer And Metastasis, Carlos Martínez-Ruiz, James R M Black, Clare Puttick, Mark S Hill, Jonas Demeulemeester, Elizabeth Larose Cadieux, Kerstin Thol, Thomas P Jones, Selvaraju Veeriah, Cristina Naceur-Lombardelli, Antonia Toncheva, Paulina Prymas, Andrew Rowan, Sophia Ward, Laura Cubitt, Foteini Athanasopoulou, Oriol Pich, Takahiro Karasaki, David A Moore, Roberto Salgado, Emma Colliver, Carla Castignani, Michelle Dietzen, Ariana Huebner, Maise Al Bakir, Miljana Tanić, Thomas B K Watkins, Emilia L Lim, Ali M Al-Rashed, Danny Lang, James Clements, Daniel E Cook, Rachel Rosenthal, Gareth A Wilson, Alexander M Frankell, Sophie De Carné Trécesson, Philip East, Nnennaya Kanu, Kevin Litchfield, Nicolai J Birkbak, Allan Hackshaw, Stephan Beck, Peter Van Loo, Mariam Jamal-Hanjani, Charles Swanton, Nicholas Mcgranahan

Faculty, Staff and Student Publications

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy1. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study2,3. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression …

Evolutionary Characterization Of Lung Adenocarcinoma Morphology In Tracerx, Takahiro Karasaki, David A Moore, Selvaraju Veeriah, Cristina Naceur-Lombardelli, Antonia Toncheva, Neil Magno, Sophia Ward, Maise Al Bakir, Thomas B K Watkins, Kristiana Grigoriadis, Ariana Huebner, Mark S Hill, Alexander M Frankell, Christopher Abbosh, Clare Puttick, Haoran Zhai, Francisco Gimeno-Valiente, Sadegh Saghafinia, Nnennaya Kanu, Michelle Dietzen, Oriol Pich, Emilia L Lim, Carlos Martínez-Ruiz, James R M Black, Dhruva Biswas, Brittany B Campbell, Claudia Lee, Emma Colliver, Katey S S Enfield, Sonya Hessey, Crispin T Hiley, Simone Zaccaria, Kevin Litchfield, Nicolai J Birkbak, Elizabeth Larose Cadieux, Jonas Demeulemeester, Peter Van Loo, Prasad S Adusumilli, Kay See Tan, Waseem Cheema, Francisco Sanchez-Vega, David R Jones, Natasha Rekhtman, William D Travis, Allan Hackshaw, Teresa Marafioti, Roberto Salgado, John Le Quesne, Andrew G Nicholson, Tracerx Consortium, Nicholas Mcgranahan, Charles Swanton, Mariam Jamal-Hanjani

Faculty, Staff and Student Publications

Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions …

The Evolution Of Non-Small Cell Lung Cancer Metastases In Tracerx, Maise Al Bakir, Ariana Huebner, Carlos Martínez-Ruiz, Kristiana Grigoriadis, Thomas B K Watkins, Oriol Pich, David A Moore, Selvaraju Veeriah, Sophia Ward, Joanne Laycock, Diana Johnson, Andrew Rowan, Maryam Razaq, Mita Akther, Cristina Naceur-Lombardelli, Paulina Prymas, Antonia Toncheva, Sonya Hessey, Michelle Dietzen, Emma Colliver, Alexander M Frankell, Abigail Bunkum, Emilia L Lim, Takahiro Karasaki, Christopher Abbosh, Crispin T Hiley, Mark S Hill, Daniel E Cook, Gareth A Wilson, Roberto Salgado, Emma Nye, Richard Kevin Stone, Dean A Fennell, Gillian Price, Keith M Kerr, Babu Naidu, Gary Middleton, Yvonne Summers, Colin R Lindsay, Fiona H Blackhall, Judith Cave, Kevin G Blyth, Arjun Nair, Asia Ahmed, Magali N Taylor, Alexander James Procter, Mary Falzon, David Lawrence, Neal Navani, Ricky M Thakrar, Sam M Janes, Dionysis Papadatos-Pastos, Martin D Forster, Siow Ming Lee, Tanya Ahmad, Sergio A Quezada, Karl S Peggs, Peter Van Loo, Caroline Dive, Allan Hackshaw, Nicolai J Birkbak, Simone Zaccaria, Tracerx Consortium, Mariam Jamal-Hanjani, Nicholas Mcgranahan, Charles Swanton

Faculty, Staff and Student Publications

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% …