Medicine and Health Sciences Commons^™

Phase 3 Trial Of 177Lu-Dotatate For Midgut Neuroendocrine Tumors, Jonathan Strosberg, Ghassan El-Haddad, Edward M. Wolin, Andrew Hendifar, James Yao, Beth Chasen, Erik Mittra, Pamela L. Kunz, Matthew H. Kulke, Heather Jacene, David Bushnell, Thomas M. O’Dorisio, Richard P. Baum, Harshad R. Kulkarni, Martyn Caplin, Rachida Lebtahi, Timothy Hobday, Ebrahim Delpassand, Eric Van Cutsem, Al Benson, Rajaventhan Srirajaskanthan, Marianne Pavel, Jaime Mora, Jordan Berlin, Enrique Grande, Nicholas Reed, Ettore Seregni, Kjell Öberg, Maribel Lopera Sierra, Paola Santoro

Markey Cancer Center Faculty Publications

BACKGROUND

Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (¹⁷⁷Lu)–Dotatate in patients with advanced, progressive, somatostatin-receptor–positive midgut neuroendocrine tumors.

METHODS

We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either ¹⁷⁷Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (¹⁷⁷Lu-Dotatate group) or octreotide LAR …

Hic1 (Hypermethylated In Cancer 1) Sumoylation Is Dispensable For Dna Repair But Is Essential For The Apoptotic Dna Damage Response (Ddr) To Irreparable Dna Double-Strand Breaks (Dsbs)., Sonia Paget, Marion Dubuissez, Vanessa Dehennaut, Joe Nassour, Brennan T Harmon, Nathalie Spruyt, Ingrid Loison, Corinne Abbadie, Brian R Rood, Dominique Leprince

Surgery Faculty Publications

The tumor suppressor gene HIC1 (Hypermethylated In Cancer 1) encodes a transcriptional repressor mediating the p53-dependent apoptotic response to irreparable DNA double-strand breaks (DSBs) through direct transcriptional repression of SIRT1. HIC1 is also essential for DSB repair as silencing of endogenous HIC1 in BJ-hTERT fibroblasts significantly delays DNA repair in functional Comet assays. HIC1 SUMOylation favours its interaction with MTA1, a component of NuRD complexes. In contrast with irreparable DSBs induced by 16-hours of etoposide treatment, we show that repairable DSBs induced by 1 h etoposide treatment do not increase HIC1 SUMOylation or its interaction with MTA1. Furthermore, HIC1 SUMOylation …

Androgen Receptor-Dependent And -Independent Mechanisms Driving Prostate Cancer Progression: Opportunities For Therapeutic Targeting From Multiple Angles., David T. Hoang, Kenneth A. Iczkowski, Deepak Kilari, William See, Marja T. Nevalainen

Student Papers, Posters & Projects

Despite aggressive treatment for localized cancer, prostate cancer (PC) remains a leading cause of cancer-related death for American men due to a subset of patients progressing to lethal and incurable metastatic castrate-resistant prostate cancer (CRPC). Organ-confined PC is treated by surgery or radiation with or without androgen deprivation therapy (ADT), while options for locally advanced and disseminated PC include radiation combined with ADT, or systemic treatments including chemotherapy. Progression to CRPC results from failure of ADT, which targets the androgen receptor (AR) signaling axis and inhibits AR-driven proliferation and survival pathways. The exact mechanisms underlying the transition from androgen-dependent PC …

Natural Compounds Targeting Major Cell Signaling Pathways: A Novel Paradigm For Osteosarcoma Therapy., Pablo Angulo, Gaurav Kaushik, Dharmalingam Subramaniam, Prasad Dandawate, Kathleen Neville, Katherine Chastain, Shrikant Anant

Manuscripts, Articles, Book Chapters and Other Papers

Osteosarcoma is the most common primary bone cancer affecting children and adolescents worldwide. Despite an incidence of three cases per million annually, it accounts for an inordinate amount of morbidity and mortality. While the use of chemotherapy (cisplatin, doxorubicin, and methotrexate) in the last century initially resulted in marginal improvement in survival over surgery alone, survival has not improved further in the past four decades. Patients with metastatic osteosarcoma have an especially poor prognosis, with only 30% overall survival. Hence, there is a substantial need for new therapies. The inability to control the metastatic progression of this localized cancer stems …

Unique Breast Cancer Features Within The Vietnamese Population, Polly Niravath, Melissa Bondy, Susan G. Hilsenbeck

Journal of Health Disparities Research and Practice

BACKGROUND: Breast cancer is known to be a heterogeneous disease across women, and even within individual tumors. However, relatively little is known about heterogeneity across cultures. There has been some evidence to suggest that Asian women are more likely to have HER2+ breast cancer than their Caucasian counterparts.

PURPOSE: The aim of this study was to further investigate the unique pattern of breast cancer incidence and subtype in the Vietnamese population.

METHODS: We retrospectively collected data on all Vietnamese women diagnosed with invasive breast cancer at the Lester & Sue Smith Breast Center in Houston, Texas over a four year …

Biological Functions Of Cdk5 And Potential Cdk5 Targeted Clinical Treatments., Alison Shupp, Mathew C. Casimiro, Richard G. Pestell

Department of Cancer Biology Faculty Papers

Cyclin dependent kinases are proline-directed serine/threonine protein kinases that are traditionally activated upon association with a regulatory subunit. For most CDKs, activation by a cyclin occurs through association and phosphorylation of the CDK's T-loop. CDK5 is unusual because it is not typically activated upon binding with a cyclin and does not require T-loop phosphorylation for activation, even though it has high amino acid sequence homology with other CDKs. While it was previously thought that CDK5 only interacted with p35 or p39 and their cleaved counterparts, Recent evidence suggests that CDK5 can interact with certain cylins, amongst other proteins, which modulate …

Increased Ros Production In Non-Polarized Mammary Epithelial Cells Induces Monocyte Infiltration In 3d Culture, Linzhang Li, Jie Chen, Gaofeng Xiong, Daret K. St. Clair, Wei Xu, Ren Xu

Markey Cancer Center Faculty Publications

Loss of epithelial cell polarity promotes cell invasion and cancer dissemination. Therefore, identification of factors that disrupt polarized acinar formation is crucial. Reactive oxygen species (ROS) drive cancer progression and promote inflammation. Here, we show that the non-polarized breast cancer cell line T4-2 generates significantly higher ROS levels than polarized S1 and T4R cells in three-dimensional (3D) culture, accompanied by induction of the nuclear factor κB (NF-κB) pathway and cytokine expression. Minimizing ROS in T4-2 cells with antioxidants reestablished basal polarity and inhibited cell proliferation. Introducing constitutively activated RAC1 disrupted cell polarity and increased ROS levels, indicating that RAC1 is …

Dynamical System Modeling To Simulate Donor T Cell Response To Whole Exome Sequencing-Derived Recipient Peptides: Understanding Randomness In Alloreactivity Incidence Following Stem Cell Transplantation, Vishal Koparde, Badar Abdul Razzaq, Tara Suntum, Roy Sabo, Allison Scalora, Myrna Serrano, Max Jameson-Lee, Charles Hall, David Kobulnicky, Nihar Sheth, Juliana Feltz, Daniel Contaifer, Dayanjan Wijesinghe, Jason Reed, Catherine Roberts, Rehan Qayyum, Gregory Buck, Michael Neale, Amir Toor

Massey Comprehensive Cancer Center Data

Quantitative relationship between the magnitude of variation in minor histocompatibility antigens (mHA) and graft versus host disease (GVHD) pathophysiology in stem cell transplant (SCT) donor-recipient pairs (DRP) is not established. In order to elucidate this relationship, whole exome sequencing (WES) was performed on 27 HLA matched related (MRD), & 50 unrelated donors (URD), to identify nonsynonymous single nucleotide polymorphisms (SNPs). An average 2,463 SNPs were identified in MRD, and 4,287 in URD DRP (p

Muc1 Facilitates Metabolomic Reprogramming In Triple-Negative Breast Cancer, Gennifer Goode, Venugopal Gunda, Nina V. Chaika, Vinee Purohit, Fang Yu, Pankaj K. Singh

Journal Articles: Eppley Institute

BACKGROUND: Mucin1 (MUC1), a glycoprotein associated with chemoresistance and an aggressive cancer phenotype, is aberrantly overexpressed in triple-negative breast cancer (TNBC). Recent studies suggest that MUC1 plays a role in modulating cancer cell metabolism and thereby supports tumor growth. Herein, we examined the role of MUC1 in metabolic reprogramming in TNBC.

METHODS: MUC1 was stably overexpressed in MDA-MB-231 TNBC cells and stably knocked down in MDA-MB-468 cells. We performed liquid chromatography-coupled tandem mass spectrometry-assisted metabolomic analyses and physiological assays, which indicated significant alterations in the metabolism of TNBC cells due to MUC1 expression.

RESULTS: Differential analyses identified significant differences in …

Doxorubicin Cytotoxicity In A Human Proximal Tubular Epithelial Cell Line Was Attenuated By The Natural Product Resveratrol, Morghan Schuyler Getty

Theses, Dissertations and Capstones

The cancer chemotherapeutic agent doxorubicin (DOX), Adriamycin, is part of the treatment regimen for breast, ovarian, small cell lung cancer and acute/chronic lymphoid leukemia. Adverse effects associated with DOX are cardiotoxicity and nephrotoxicity. Interventions are needed to reduce DOX nephrotoxicity. Resveratrol (RES) is a phytochemical contained in grapes, berries and nuts, which possesses antioxidant and anticancer properties. This study tested the hypothesis that RES will attenuate DOX renal cytotoxicity in human noncancerous renal proximal tubular epithelial (HK-2) cells and that RES will reduce DOX mediated changes in mitochondrial function. HK-2 cells were plated and grown for 48 hours (h). Cells …

Inhibiting Dna Methylation Activates Cancer Testis Antigens And Expression Of The Antigen Processing And Presentation Machinery In Colon And Ovarian Cancer Cells., Cornelia Siebenkäs, Katherine B Chiappinelli, Angela A Guzzetta, Anup Sharma, Jana Jeschke, Rajita Vatapalli, Stephen B Baylin, Nita Ahuja

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Innovative therapies for solid tumors are urgently needed. Recently, therapies that harness the host immune system to fight cancer cells have successfully treated a subset of patients with solid tumors. These responses have been strong and durable but observed in subsets of patients. Work from our group and others has shown that epigenetic therapy, specifically inhibiting the silencing DNA methylation mark, activates immune signaling in tumor cells and can sensitize to immune therapy in murine models. Here we show that colon and ovarian cancer cell lines exhibit lower expression of transcripts involved in antigen processing and presentation to immune cells …

Repurposing Mebendazole As A Replacement For Vincristine For The Treatment Of Brain Tumors, M. De Witt, A. Gamble, D. Hanson, D. Markowitz, C. Powell, S. Al Dimassi, M. Atlas, J. Boockvar, R. Ruggieri, M. Symons

Journal Articles

No abstract provided.

Cancer Care Annual Report 2016-2017, Children's Mercy Hospital

Cancer Center Annual Reports

Annual report of cancer care and oncology services at the Children's Mercy Hospital, Kansas City MO, a pediatric medical center. This report has a focus on sarcomas.

Glypican-3 And Cd81 Promote Development Of Hepatocellular Carcinoma And Hepatoblastoma Through Negative Selection., Yuhua Xue, Wendy Mars, William Bowen, Aatur D. Singhi, Sarangarajan Ranganathan, George K. Michalopoulos

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Prophylactic Use Of Metformin To Decrease The Incidence Of Breast Cancer In High Risk, Predisposed Women, Aly Dahl

Physician Assistant Scholarly Project Posters

• Breast cancer is one of the most common types of cancer in American women and is the second leading cause of mortality.

• In 2015, 234,190 new diagnoses were made and 40,730 deaths from breast cancer.

• Along with a thorough history from the patient, there are also several risk assessment models that should be utilized, such as the common Gail-2 model.

• Any women with a significant family history should also be educated on genetic counseling and/or testing to detect a BRCA1 or 2 mutation.

• Numerous individuals who are positive for this gene elect to undergo prophylactic …

Human Cytomegalovirus Interleukin-10 Enhances Matrigel Invasion Of Mda-Mb-231 Breast Cancer Cells, Cendy Valle Oseguera, Juliet Spencer

Biology Faculty Publications

Background: While some risk factors for breast cancer are well-known, the influence of other factors, particularly virus infection, remains unclear. Human cytomegalovirus (HCMV) is widespread in the general population, and both molecular and epidemiological evidence has indicated links between HCMV and breast cancer. The HCMV protein cmvIL-10 is a potent suppressor of immune function that has also been shown to promote proliferation and migration of breast cancer cells. In this study, the impact of cmvIL-10 on tumor cell invasion through a simulated basement membrane was investigated.

Results: MDA-MB-231 breast cancer cells exhibited invasion through a matrigel layer that was significantly …

Malignant Peripheral Nerve Sheath Tumors State Of The Science: Leveraging Clinical And Biological Insights Into Effective Therapies., Aerang Kim, Douglas R Stewart, Karlyne M Reilly, David Viskochil, Markku M Miettinen, Brigitte C Widemann

Pediatrics Faculty Publications

Malignant peripheral nerve sheath tumor (MPNST) is the leading cause of mortality in patients with neurofibromatosis type 1. In 2002, an MPNST consensus statement reviewed the current knowledge and provided guidance for the diagnosis and management of MPNST. Although the improvement in clinical outcome has not changed, substantial progress has been made in understanding the natural history and biology of MPNST through imaging and genomic advances since 2002. Genetically engineered mouse models that develop MPNST spontaneously have greatly facilitated preclinical evaluation of novel drugs for translation into clinical trials led by consortia efforts. Continued work in identifying alterations that contribute …

Employing The Enzyme Cofactor Function Of Ascorbic Acid To Affect Oncogenic Pathways In Human Melanoma: Modulating Hypoxia Inducible Factor-1Α And Dna Demethylation To Reduce Malignant Potential, Adam Patrick Fischer

Theses, Dissertations and Capstones

Dioxygenase enzymes such as the HIF hydroxylases (PHD1-3, FIH) and the Ten-eleven translocation (TET1-3) enzymes regulate the activity of the hypoxia inducible factor-1_a (HIF1_a) transcription factor and the DNA methylation status of cells, respectively. Aberrant accumulation and activation of HIF-1_a can allow malignant cells to acquire attributes that promote progression, chemotherapy resistance, and survival, while aberrant hypermethylation of gene promoters can silence the expression of tumor suppressor genes essential to preventing tumorigenesis. Inadequate levels of intracellular ascorbic acid (AA), a necessary cofactor for optimal dioxygenase enzyme function, could potentiate these tumorigenic conditions. In fact, plasma levels …

Genetic Polymorphisms In Caveolin-1 Associate With Breast Cancer Risk In Chinese Han Population, M Wang, T Tian, X Ma, W Zhu, Y Guo, Z Duan, J Fan, S Lin, K Liu, Y Zheng, Q Sheng, Z J. Dai, H Peng

Biochemistry and Molecular Medicine Faculty Publications

Caveolin-1(CAV-1) was demonstrated to be a tumor suppressor gene and be implicated in the development of breast cancer (BC). Numerous potentially functional polymorphisms in CAV-1 have been identified, but their effects on BC were not clear. This case-control study aims to evaluate the relationship between CAV-1 polymorphisms and BC risk. 560 BC patients and 583 healthy controls were enrolled in the present study, all from Chinese Han population. We detected 3 single nucleotide polymorphisms (rs3807987, rs1997623, and rs7804372) in CAV-1 using the Sequenom MassARRAY method. The association between CAV-1genotypes and BC risk was assessed in six genetic …

Anti-Cancer Effects Of Tocotrienols In Nsclc, Lichchavi Raj Raj

Wayne State University Dissertations

Lung cancer is one of the leading causes of death among cancers, with non-small cell lung cancer (NSCLC) accounting for 80-85% of all lung cancers and a five-year survival rate of 5 % at stage IIIB. Delta-tocotrienol (δT) including other tocotrienol isomers has been shown to exhibit anti-tumor activity via inhibition of different signaling pathways in tumors including NSCLC. Previously we reported that δT reduced cell invasion via inhibition of the Notch-1 and NF-κb pathway.

Matrix metallopeptidase 9 (MMP9) dependent cell migration and invasion are key processes in cancer metastasis. Hence, its suppression is a promising strategy for cancer therapeutics. …

Ptpro Represses Erbb2-Driven Breast Oncogenesis By Dephosphorylation And Endosomal Internalization Of Erbb2., H Dong, L Ma, J Gan, W Lin, Rakesh Kumar, +9 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

The plasma membrane-associated tyrosine phosphatase PTPRO is frequently transcriptionally repressed in cancers and signifies poor prognosis of breast cancer patients. In this study, deletion of Ptpro inMMTV-Erbb2 transgenic mice dramatically shortened the mammary tumor latency and accelerated tumor growth due to loss of Ptpro within the breast cancer cells but not in surrounding tissue as confirmed by hetero-transplantation studies. Both in vitro and in vivo data demonstrated that the phosphatase activity was required for the inactivation of ERBB2 and its downstream signaling. PTPRO regulated the phosphorylation status of ERBB2 at Y1248. Co-immunoprecipitation and proximity ligation assay (Duolink) indicated that …

Foxc1 Is Associated With Estrogen Receptor Alpha And Affects Sensitivity Of Tamoxifen Treatment In Breast Cancer., Jinhua Wang, Yali Xu, Li Li, Lin Wang, Ru Yao, Qiang Sun, Guanhua Du

Articles, Abstracts, and Reports

FOXC1 is a member of Forkhead box transcription factors that participates in embryonic development and tumorigenesis. Our previous study demonstrated that FOXC1 was highly expressed in triple-negative breast cancer. However, it remains unclear what is the relation between FOXC1 and ERα and if FOXC1 regulates expression of ERα. To explore relation between FOXC1 and ERα and discover regulation of ERα expression by FOXC1 in breast cancer, we analyzed data assembled in the Oncomine and TCGA, and found that there was significantly higher FOXC1 expression in estrogen receptor-negative breast cancer than that in estrogen receptor-positive breast cancer. Overexpression of FOXC1 reduced …

Sting Expression And Response To Treatment With Sting Ligands In Premalignant And Malignant Disease., Jason R Baird, Zipei Feng, Hong D Xiao, David Friedman, Ben Cottam, Bernard A Fox, Gwen Kramer, Rom S Leidner, Richard Bryan Bell, Kristina H Young, Marka R Crittenden, Michael J Gough

Articles, Abstracts, and Reports

Human papilloma virus positive (HPV+) tumors represent a large proportion of anal, vulvar, vaginal, cervical and head and neck squamous carcinomas (HNSCC) and late stage invasive disease is thought to originate from a premalignant state. Cyclic dinucleotides that activate STimulator of INterferon Genes (STING) have been shown to cause rapid regression of a range of advanced tumors. We aimed to investigate STING ligands as a novel treatment for papilloma. We tested therapies in a spontaneous mouse model of papilloma of the face and anogenital region that histologically resembles human HPV-associated papilloma. We demonstrate that STING ligands cause rapid regression of …

The Effects Of Bone Marrow Adipocytes On Metabolic Regulation In Metastatic Prostate Cancer, Jonathan Diedrich

Wayne State University Dissertations

Bone is a preferential site of metastasis from prostate cancer (PCa). Although there have been many advances in therapeutic options for patients suffering from metastatic PCa, this disease remains incurable with an estimated five-year survival of 33%. To design effective therapeutic interventions for metastatic PCa, it is essential that we elucidate the molecular mechanisms responsible for tumor cell adaptation to and the ability to thrive within the bone metastatic niche. Age and obesity, conditions that increase adipocyte numbers in bone marrow, are risk factors for skeletal metastases from PCa; therefore, our laboratory is focused on the interactions between marrow adipocytes …

The Distinct Metabolic Phenotype Of Lung Squamous Cell Carcinoma Defines Selective Vulnerability To Glycolytic Inhibition, Justin Goodwin, Michael L. Neugent, Shin Yup Lee, Joshua H. Choe, Hyunsung Choi, Dana M. R. Jenkins, Robin J. Ruthenborg, Maddox W. Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D. Minna, Kristi L. Helke, Pankaj K. Singh, David B. Shackelford, Jung-Whan Kim

Journal Articles: Eppley Institute

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, …

Genomic Alterations In Mucins Across Cancers, Ryan King, Fang Yu, Pankaj K. Singh

Journal Articles: Eppley Institute

The significance of mucins in cancers has led to the development of novel biomarkers and therapeutic agents against cancers. Despite significant advances in the understanding of mucins, systemic investigations into the role of mucins in cancer biology focusing particularly on the histological subtypes and stages, along with other variables, are yet to be carried out to discover potential novel functions and cancer-specific roles. Here, we investigated 11 mucin expressing cancers for DNA mutations, mRNA expression, copy number, methylation, and the impacts these genomic features may have on patient survival by utilizing The Cancer Genome Atlas dataset. We demonstrate that mucin …

An Rnai Screen To Identify Components Of A Polyamine Transport System, Adam J. Foley

Honors Undergraduate Theses

Polyamines, specifically putrescine, spermidine, and spermine, are small cationic molecules found in all organisms. Cells can biosynthetically make these molecules, or alternatively, they can be transported from the extracellular environment. Malignant cells have been shown to require relatively high amounts of polyamines. There is a chemotherapeutic agent, DFMO, used to block the biosynthesis of polyamines. Many malignant cells can circumvent DFMO therapy by activating their transport system. A potential solution is to simultaneously block biosynthesis and transport of polyamines. However, little is known about the polyamine transport system in higher eukaryotes.

This thesis aims to add to the basic biological …

Intimate Partner Violence And Women's Cancer Quality Of Life, Ann L. Coker, Diane R. Follingstad, Lisandra S. Garcia, Heather M. Bush

CRVAW Faculty Journal Articles

Purpose

Because intimate partner violence (IPV) may disproportionately impact women’s quality of life (QOL) when undergoing cancer treatment, women experiencing IPV were hypothesized to have (a) more symptoms of depression or stress and (b) lower QOL as measured with the Functional Assessment of Cancer Therapy (FACT-B) and Functional Assessment of Chronic Illness Therapy—Spiritual Well-being (FACIT-SP) Scales relative to those never experiencing IPV.

Methods

Women, aged 18–79, who were included in one of two state cancer registries from 2009 to 2015 with a recent incident, primary, invasive biopsy-confirmed cancer diagnosis were recruited and asked to complete a phone interview, within 12 …

Disparities In Stage-Appropriate Therapy For Resectable Non-Small Cell Lung Cancer In Kentucky, Jeremiah T. Martin

Theses and Dissertations--Clinical Research Design

Lung cancer (NSCLC) is the leading cause of cancer related mortality. Lung cancer screening aims to detect treatable cancers, however survival advantage will only be seen with early and appropriate stage-directed therapy. This study aims to understand recent rates of therapy for early-stage lung cancer in Kentucky, and to explore potential sources of disparities in treatment and outcomes. A Kentucky Cancer Registry query was performed of all NSCLC cases treated in the state from 2005-2014. Of 39,763 lung cancer patients, 10,622 were clinically operable. Of these, overall 40% did not receive surgery, while 16% did not receive any stage-appropriate local …

Early Mutation Bursts In Colorectal Tumors., Junsong Zhao, Matthew P Salomon, Darryl Shibata, Christina Curtis, Kimberly Siegmund, Paul Marjoram

Articles, Abstracts, and Reports

Tumor growth is an evolutionary process involving accumulation of mutations, copy number alterations, and cancer stem cell (CSC) division and differentiation. As direct observation of this process is impossible, inference regarding when mutations occur and how stem cells divide is difficult. However, this ancestral information is encoded within the tumor itself, in the form of intratumoral heterogeneity of the tumor cell genomes. Here we present a framework that allows simulation of these processes and estimation of mutation rates at the various stages of tumor development and CSC division patterns for single-gland sequencing data from colorectal tumors. We parameterize the mutation …