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2. A Phase Ib Study Assessing the Safety, Tolerability, and Efficacy of the First-in-Class Wee1 Inhibitor Adavosertib (AZD1775) as Monotherapy in Patients with Advanced Solid Tumors

Author

Bauer, Todd M., Moore, Kathleen N., Rader, Janet S., Simpkins, Fiona, Mita, Alain C., Beck, J. Thaddeus, Hart, Lowell, Chu, Quincy, Oza, Amit, Tinker, Anna V., Imedio, Esteban Rodrigo, Kumar, Sanjeev, Mugundu, Ganesh, Jenkins, Suzanne, Chmielecki, Juliann, Jones, Suzanne, Spigel, David, and Fu, Siqing

Published
2023
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4. Analysis of Ugandan cervical carcinomas identifies human papillomavirus clade-specific epigenome and transcriptome landscapes.

Author

Gagliardi, Alessia, Porter, Vanessa L, Zong, Zusheng, Bowlby, Reanne, Titmuss, Emma, Namirembe, Constance, Griner, Nicholas B, Petrello, Hilary, Bowen, Jay, Chan, Simon K, Culibrk, Luka, Darragh, Teresa M, Stoler, Mark H, Wright, Thomas C, Gesuwan, Patee, Dyer, Maureen A, Ma, Yussanne, Mungall, Karen L, Jones, Steven JM, Nakisige, Carolyn, Novik, Karen, Orem, Jackson, Origa, Martin, Gastier-Foster, Julie M, Yarchoan, Robert, Casper, Corey, Mills, Gordon B, Rader, Janet S, Ojesina, Akinyemi I, Gerhard, Daniela S, Mungall, Andrew J, and Marra, Marco A

Subjects
Humans, Papillomaviridae, Papillomavirus Infections, Signal Transduction, DNA Methylation, Up-Regulation, Adult, Aged, Middle Aged, Uganda, Uterine Cervical Neoplasms, Female, Promoter Regions, Genetic, Transcriptome, Epigenome, Promoter Regions, Genetic, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Cervical cancer is the most common cancer affecting sub-Saharan African women and is prevalent among HIV-positive (HIV+) individuals. No comprehensive profiling of cancer genomes, transcriptomes or epigenomes has been performed in this population thus far. We characterized 118 tumors from Ugandan patients, of whom 72 were HIV+, and performed extended mutation analysis on an additional 89 tumors. We detected human papillomavirus (HPV)-clade-specific differences in tumor DNA methylation, promoter- and enhancer-associated histone marks, gene expression and pathway dysregulation. Changes in histone modification at HPV integration events were correlated with upregulation of nearby genes and endogenous retroviruses.

Published
2020

5. The Immune Landscape of Cancer

Author

Thorsson, Vésteinn, Gibbs, David L, Brown, Scott D, Wolf, Denise, Bortone, Dante S, Yang, Tai-Hsien Ou, Porta-Pardo, Eduard, Gao, Galen F, Plaisier, Christopher L, Eddy, James A, Ziv, Elad, Culhane, Aedin C, Paull, Evan O, Sivakumar, IK Ashok, Gentles, Andrew J, Malhotra, Raunaq, Farshidfar, Farshad, Colaprico, Antonio, Parker, Joel S, Mose, Lisle E, Vo, Nam Sy, Liu, Jianfang, Liu, Yuexin, Rader, Janet, Dhankani, Varsha, Reynolds, Sheila M, Bowlby, Reanne, Califano, Andrea, Cherniack, Andrew D, Anastassiou, Dimitris, Bedognetti, Davide, Mokrab, Younes, Newman, Aaron M, Rao, Arvind, Chen, Ken, Krasnitz, Alexander, Hu, Hai, Malta, Tathiane M, Noushmehr, Houtan, Pedamallu, Chandra Sekhar, Bullman, Susan, Ojesina, Akinyemi I, Lamb, Andrew, Zhou, Wanding, Shen, Hui, Choueiri, Toni K, Weinstein, John N, Guinney, Justin, Saltz, Joel, Holt, Robert A, Rabkin, Charles S, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, and Broom, Bradley M

Subjects
Biomedical and Clinical Sciences, Immunology, Cancer Genome Atlas Research Network
Abstract

(Immunity 48, 812–830.e1–e14; April 17, 2018) In the originally published version of this article, the authors neglected to include Younes Mokrab and Aaron M. Newman as co-authors and misspelled the names of authors Charles S. Rabkin and Ilya Shmulevich. The author names have been corrected here and online. In addition, the concluding sentence of the subsection “Immune Signature Compilation” in the Method Details in the original published article was deemed unclear because it did not specify differences among the gene set scoring methods. The concluding sentences now reads “Gene sets from Bindea et al., Senbabaoglu et al., and the MSigDB C7 collection were scored using single-sample gene set enrichment (ssGSEA) analysis (Barbie et al., 2009), as implemented in the GSVA R package (Hänzelmann et al., 2013). All other signatures were scored using methods found in the associated citations.”

Published
2019

6. GOG 8020/210: Risk stratification of lymph node metastasis, disease progression and survival using single nucleotide polymorphisms in endometrial cancer: An NRG oncology/gynecologic oncology group study

Author

Brooks, Rebecca A, Tritchler, David S, Darcy, Kathleen M, Lankes, Heather A, Salani, Ritu, Sperduto, Paul, Guntupalli, Saketh, DiSilvestro, Paul, Kesterson, Joshua, Olawaiye, Alexander B, Moxley, Katherine, Waggoner, Steven, Santin, Alessandro, Rader, Janet S, Kizer, Nora T, Thaker, Premal H, Powell, Matthew A, Mutch, David G, Birrer, Michael J, and Goodfellow, Paul J

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Cancer, Clinical Research, Genetics, Patient Safety, Uterine Cancer, 2.1 Biological and endogenous factors, Aetiology, Aged, Biomarkers, Tumor, Case-Control Studies, Disease Progression, Endometrial Neoplasms, Endometrium, ErbB Receptors, Female, Humans, Lymphatic Metastasis, Middle Aged, NM23 Nucleoside Diphosphate Kinases, Neoplasm Staging, Polymorphism, Single Nucleotide, Prognosis, Progression-Free Survival, Risk Assessment, Endometrial cancer, Risk stratification, SNP association, Node positivity, Paediatrics and Reproductive Medicine, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis, Reproductive medicine
Abstract

ObjectivesThe ability to stratify a patient's risk of metastasis and survival permits more refined care. A proof of principle study was undertaken to investigate the relationship between single nucleotide polymorphisms (SNPs) in literature based candidate cancer genes and the risk of nodal metastasis and clinical outcome in endometrioid endometrial cancer (EEC) patients.MethodsSurgically-staged EEC patients from the Gynecologic Oncology Group or Washington University School of Medicine with germline DNA available were eligible. Fifty-four genes represented by 384 SNPs, were evaluated by Illumina Custom GoldenGate array. Association with lymph node metastases was the primary outcome. Progression-free survival (PFS) and overall survival (OS) was also evaluated.Results361 SNPs with high quality genotype data were evaluated in 337 patients with outcome data. Five SNPs in CXCR2 had an odds ratio (OR) between 0.68 and 0.70 (p-value ≤ 0.025). The A allele rs946486 in ABL had an OR of 1.5 (p-value = 0.01) for metastasis. The G allele in rs7795743 in EGFR had an OR for metastasis of 0.68 (p-value = 0.02) and hazard ratio (HR) for progression of 0.66 (p-value = 0.004). Importantly, no SNP met genome wide significance after adjusting for multiple test correcting and clinical covariates. The A allele in rs2159359 SNP in NME1 and the G allele in rs13222385 in EGFR were associated with worse OS. Both exhibited genome wide significance; rs13222385 remained significant after adjusting for prognostic clinical variables.ConclusionSNPs in cancer genes including rs2159359 SNP in NME1 and rs13222385 in EGFR may stratify risk in EEC and are prioritized for further investigation.

Published
2019

8. Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

Author

Campbell, Joshua D, Yau, Christina, Bowlby, Reanne, Liu, Yuexin, Brennan, Kevin, Fan, Huihui, Taylor, Alison M, Wang, Chen, Walter, Vonn, Akbani, Rehan, Byers, Lauren Averett, Creighton, Chad J, Coarfa, Cristian, Shih, Juliann, Cherniack, Andrew D, Gevaert, Olivier, Prunello, Marcos, Shen, Hui, Anur, Pavana, Chen, Jianhong, Cheng, Hui, Hayes, D Neil, Bullman, Susan, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Sadeghi, Sara, Mungall, Karen L, Robertson, A Gordon, Benz, Christopher, Schultz, Andre, Kanchi, Rupa S, Gay, Carl M, Hegde, Apurva, Diao, Lixia, Wang, Jing, Ma, Wencai, Sumazin, Pavel, Chiu, Hua-Sheng, Chen, Ting-Wen, Gunaratne, Preethi, Donehower, Larry, Rader, Janet S, Zuna, Rosemary, Al-Ahmadie, Hikmat, Lazar, Alexander J, Flores, Elsa R, Tsai, Kenneth Y, Zhou, Jane H, Rustgi, Anil K, Drill, Esther, Shen, Ronglei, Wong, Christopher K, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, and Zhang, Wei

Subjects
Biological Sciences, Infectious Diseases, Cancer, Sexually Transmitted Infections, Cancer Genomics, Genetics, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Carcinoma, Squamous Cell, Cell Line, Tumor, DNA Methylation, Epithelial-Mesenchymal Transition, Gene Expression Regulation, Neoplastic, Genomics, Humans, Metabolic Networks and Pathways, Polymorphism, Genetic, Cancer Genome Atlas Research Network, bladder carcinoma with squamous differentiation, cervical squamous cell carcinoma, esophageal squamous cell carcinoma, genomics, head and neck squamous cell carcinoma, human papillomavirus, lung squamous cell carcinoma, proteomics, transcriptomics, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs), DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation. Low-CNA SCCs tended to be HPV(+) and display hypermethylation with repression of TET1 demethylase and FANCF, previously linked to predisposition to SCC, or harbor mutations affecting CASP8, RAS-MAPK pathways, chromatin modifiers, and immunoregulatory molecules. We uncovered hypomethylation of the alternative promoter that drives expression of the ΔNp63 oncogene and embedded miR944. Co-expression of immune checkpoint, T-regulatory, and Myeloid suppressor cells signatures may explain reduced efficacy of immune therapy. These findings support possibilities for molecular classification and therapeutic approaches.

Published
2018

9. The Immune Landscape of Cancer

Author

Thorsson, Vésteinn, Gibbs, David L, Brown, Scott D, Wolf, Denise, Bortone, Dante S, Ou Yang, Tai-Hsien, Porta-Pardo, Eduard, Gao, Galen F, Plaisier, Christopher L, Eddy, James A, Ziv, Elad, Culhane, Aedin C, Paull, Evan O, Sivakumar, IK Ashok, Gentles, Andrew J, Malhotra, Raunaq, Farshidfar, Farshad, Colaprico, Antonio, Parker, Joel S, Mose, Lisle E, Vo, Nam Sy, Liu, Jianfang, Liu, Yuexin, Rader, Janet, Dhankani, Varsha, Reynolds, Sheila M, Bowlby, Reanne, Califano, Andrea, Cherniack, Andrew D, Anastassiou, Dimitris, Bedognetti, Davide, Mokrab, Younes, Newman, Aaron M, Rao, Arvind, Chen, Ken, Krasnitz, Alexander, Hu, Hai, Malta, Tathiane M, Noushmehr, Houtan, Pedamallu, Chandra Sekhar, Bullman, Susan, Ojesina, Akinyemi I, Lamb, Andrew, Zhou, Wanding, Shen, Hui, Choueiri, Toni K, Weinstein, John N, Guinney, Justin, Saltz, Joel, Holt, Robert A, Rabkin, Charles S, Lazar, Alexander J, Serody, Jonathan S, Demicco, Elizabeth G, Disis, Mary L, Vincent, Benjamin G, Shmulevich, Ilya, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan Julia, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, and Reynolds, Sheila

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cancer, Immunotherapy, Cancer Genomics, Genetics, Human Genome, 2.1 Biological and endogenous factors, Inflammatory and immune system, Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Genomics, Humans, Interferon-gamma, Macrophages, Male, Middle Aged, Neoplasms, Prognosis, Th1-Th2 Balance, Transforming Growth Factor beta, Wound Healing, Young Adult, Cancer Genome Atlas Research Network, cancer genomics, immune subtypes, immuno-oncology, immunomodulatory, immunotherapy, integrative network analysis, tumor immunology, tumor microenvironment
Abstract

We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant-characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field.

Published
2018

10. A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers

Author

Berger, Ashton C, Korkut, Anil, Kanchi, Rupa S, Hegde, Apurva M, Lenoir, Walter, Liu, Wenbin, Liu, Yuexin, Fan, Huihui, Shen, Hui, Ravikumar, Visweswaran, Rao, Arvind, Schultz, Andre, Li, Xubin, Sumazin, Pavel, Williams, Cecilia, Mestdagh, Pieter, Gunaratne, Preethi H, Yau, Christina, Bowlby, Reanne, Robertson, A Gordon, Tiezzi, Daniel G, Wang, Chen, Cherniack, Andrew D, Godwin, Andrew K, Kuderer, Nicole M, Rader, Janet S, Zuna, Rosemary E, Sood, Anil K, Lazar, Alexander J, Ojesina, Akinyemi I, Adebamowo, Clement, Adebamowo, Sally N, Baggerly, Keith A, Chen, Ting-Wen, Chiu, Hua-Sheng, Lefever, Steve, Liu, Liang, MacKenzie, Karen, Orsulic, Sandra, Roszik, Jason, Shelley, Carl Simon, Song, Qianqian, Vellano, Christopher P, Wentzensen, Nicolas, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Ju, Zhenlin, Li, Jun, Liang, Han, and Ling, Shiyun

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Women's Health, Cancer, Cancer Genomics, Precision Medicine, Genetics, Human Genome, Breast Cancer, 4.1 Discovery and preclinical testing of markers and technologies, Breast Neoplasms, DNA Copy Number Variations, Databases, Genetic, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Genetic Predisposition to Disease, Genital Neoplasms, Female, Humans, Mutation, Organ Specificity, Prognosis, RNA, Long Noncoding, Receptors, Estrogen, Cancer Genome Atlas Research Network, TCGA, The Cancer Genome Atlas, breast cancer, cervical cancer, gynecologic cancer, omics, ovarian cancer, pan-gynecologic, uterine cancer, uterine carcinosarcoma, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories.

Published
2018

11. RNA-binding protein FXR1 drives cMYC translation by recruiting eIF4F complex to the translation start site

Author

George, Jasmine, Li, Yongsheng, Kadamberi, Ishaque P., Parashar, Deepak, Tsaih, Shirng-Wern, Gupta, Prachi, Geethadevi, Anjali, Chen, Changliang, Ghosh, Chandrima, Sun, Yunguang, Mittal, Sonam, Ramchandran, Ramani, Rui, Hallgeir, Lopez-Berestein, Gabriel, Rodriguez-Aguayo, Cristian, Leone, Gustavo, Rader, Janet S., Sood, Anil K., Dey, Madhusudan, Pradeep, Sunila, and Chaluvally-Raghavan, Pradeep

Published
2021
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13. Integrated genomic and molecular characterization of cervical cancer

Author

Burk, Robert D, Chen, Zigui, Saller, Charles, Tarvin, Katherine, Carvalho, Andre L, Scapulatempo-Neto, Cristovam, Silveira, Henrique C, Fregnani, José H, Creighton, Chad J, Anderson, Matthew L, Castro, Patricia, Wang, Sophia S, Yau, Christina, Benz, Christopher, Robertson, A Gordon, Mungall, Karen, Lim, Lynette, Bowlby, Reanne, Sadeghi, Sara, Brooks, Denise, Sipahimalani, Payal, Mar, Richard, Ally, Adrian, Clarke, Amanda, Mungall, Andrew J, Tam, Angela, Lee, Darlene, Chuah, Eric, Schein, Jacqueline E, Tse, Kane, Kasaian, Katayoon, Ma, Yussanne, Marra, Marco A, Mayo, Michael, Balasundaram, Miruna, Thiessen, Nina, Dhalla, Noreen, Carlsen, Rebecca, Moore, Richard A, Holt, Robert A, Jones, Steven JM, Wong, Tina, Pantazi, Angeliki, Parfenov, Michael, Kucherlapati, Raju, Hadjipanayis, Angela, Seidman, Jonathan, Kucherlapati, Melanie, Ren, Xiaojia, Xu, Andrew W, Yang, Lixing, Park, Peter J, Lee, Semin, Rabeno, Brenda, Huelsenbeck-Dill, Lori, Borowsky, Mark, Cadungog, Mark, Iacocca, Mary, Petrelli, Nicholas, Swanson, Patricia, Ojesina, Akinyemi I, Le, Xuan, Sandusky, George, Adebamowo, Sally N, Akeredolu, Teniola, Adebamowo, Clement, Reynolds, Sheila M, Shmulevich, Ilya, Shelton, Candace, Crain, Daniel, Mallery, David, Curley, Erin, Gardner, Johanna, Penny, Robert, Morris, Scott, Shelton, Troy, Liu, Jia, Lolla, Laxmi, Chudamani, Sudha, Wu, Ye, Birrer, Michael, McLellan, Michael D, Bailey, Matthew H, Miller, Christopher A, Wyczalkowski, Matthew A, Fulton, Robert S, Fronick, Catrina C, Lu, Charles, Mardis, Elaine R, Appelbaum, Elizabeth L, Schmidt, Heather K, Fulton, Lucinda A, Cordes, Matthew G, Li, Tiandao, Ding, Li, Wilson, Richard K, Rader, Janet S, Behmaram, Behnaz, Uyar, Denise, and Bradley, William

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cervical Cancer, Cancer, Clinical Research, Human Genome, Sexually Transmitted Infections, Biotechnology, Genetics, 2.1 Biological and endogenous factors, Aetiology, APOBEC-1 Deaminase, Adenocarcinoma, B7-H1 Antigen, Carcinoma, Squamous Cell, Caspase 8, DNA-Binding Proteins, Female, Genomics, HLA-A Antigens, Human papillomavirus 16, Humans, Keratins, Mitogen-Activated Protein Kinase Kinases, Molecular Targeted Therapy, Mutation, Nuclear Proteins, PTEN Phosphohydrolase, Phosphatidylinositol 3-Kinases, Programmed Cell Death 1 Ligand 2 Protein, Protein Serine-Threonine Kinases, Proteomics, Proto-Oncogene Proteins p21(ras), RNA, Long Noncoding, Receptor, ErbB-3, Receptor, Transforming Growth Factor-beta Type II, Receptors, Transforming Growth Factor beta, Signal Transduction, Transcription Factors, Uterine Cervical Neoplasms, Virus Integration, Cancer Genome Atlas Research Network, Albert Einstein College of Medicine, Analytical Biological Services, Barretos Cancer Hospital, Baylor College of Medicine, Beckman Research Institute of City of Hope, Buck Institute for Research on Aging, Canada's Michael Smith Genome Sciences Centre, Harvard Medical School, Helen F. Graham Cancer Center &Research Institute at Christiana Care Health Services, HudsonAlpha Institute for Biotechnology, ILSbio, LLC, Indiana University School of Medicine, Institute of Human Virology, Institute for Systems Biology, International Genomics Consortium, Leidos Biomedical, Massachusetts General Hospital, McDonnell Genome Institute at Washington University, Medical College of Wisconsin, Medical University of South Carolina, Memorial Sloan Kettering Cancer Center, Montefiore Medical Center, NantOmics, National Cancer Institute, National Hospital, Abuja, Nigeria, National Human Genome Research Institute, National Institute of Environmental Health Sciences, National Institute on Deafness &Other Communication Disorders, Ontario Tumour Bank, London Health Sciences Centre, Ontario Tumour Bank, Ontario Institute for Cancer Research, Ontario Tumour Bank, The Ottawa Hospital, Oregon Health &Science University, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, SRA International, St Joseph's Candler Health System, Eli &Edythe L. Broad Institute of Massachusetts Institute of Technology &Harvard University, Research Institute at Nationwide Children's Hospital, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, University of Bergen, University of Texas MD Anderson Cancer Center, University of Abuja Teaching Hospital, University of Alabama at Birmingham, University of California, Irvine, University of California Santa Cruz, University of Kansas Medical Center, University of Lausanne, University of New Mexico Health Sciences Center, University of North Carolina at Chapel Hill, University of Oklahoma Health Sciences Center, University of Pittsburgh, University of São Paulo, Ribeir ão Preto Medical School, University of Southern California, University of Washington, University of Wisconsin School of Medicine &Public Health, Van Andel Research Institute, Washington University in St Louis, Receptor, erbB-3, General Science & Technology
Abstract

Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers.

Published
2017

14. Deciphering the divergent transcriptomic landscapes of cervical cancer cells grown in 3D and 2D cell culture systems.

Author

Kumar, Roshan, Iden, Marissa, Tsaih, Shirng-Wern, Schmidt, Rachel, Ojesina, Akinyemi I., and Rader, Janet S.

Subjects
CERVICAL cancer, CELL culture, CANCER cells, GENE expression, VIRAL genes
Abstract

Cervical cancer remains a significant health challenge for women worldwide, with a disproportionate impact on developing regions like sub-Saharan Africa. Taking advantage of recent advancements in developing suitable preclinical models to study cell proliferation, differentiation, and gene expression, we used RNA sequencing to compare the transcriptomic profiles of SiHa cervical cancer cells grown in 3D versus 2D culture systems. Pathway analysis of 3D cultures revealed upregulation of immune activation, angiogenesis, and tissue remodeling pathways. The high expression of cytokines, chemokines, matrix metalloproteinases, and immediate early genes, suggests that 3D cultures replicate the tumor microenvironment better than 2D monolayer cultures. HPV gene expression analysis further demonstrated higher expression levels of HPV16 E1, E2, E6, and E7 genes in 3D versus 2D cultures. Further, by using a set of linear models, we identified 79 significantly differentially expressed genes in 3D culture compared to 2D culture conditions, independent of HPV16 viral gene effects. We subsequently validated five of these genes at the protein level in both the SiHa cell line and a newly developed, patient-derived cervical cancer cell line. In addition, correlation analysis identified 26 human genes positively correlated with viral genes across 2D and 3D culture conditions. The top five 3D versus 2D differentially expressed and HPV-correlated genes were validated via qRT-PCR in our patient derived cell line. Altogether, these findings suggest that 3D cultures provide superior model systems to explore mechanisms of immune evasion, cancer progression and antiviral therapeutics. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Landscape of potential germline pathogenic variants in select cancer susceptibility genes in patients with adult‐type ovarian granulosa cell tumors.

Author

Summey, Rebekah M., Gornstein, Erica, Decker, Brennan, Dougherty, Kali C., Rader, Janet S., and Hopp, Elizabeth

Subjects
GRANULOSA cell tumors, CANCER genes, CANCER susceptibility, DISEASE susceptibility, SINGLE nucleotide polymorphisms, GERM cells, OOGENESIS
Abstract

Objective: The objective of this study was to assess the frequency of potential germline pathogenic variants that may contribute to risk of development of adult granulosa cell tumors (AGCT) given the paucity of germline testing guidelines for these patients. Methods: This was a retrospective cross‐sectional study analyzing comprehensive genomic profiling (CGP) results of AGCT with the FOXL2 p.C134W mutation submitted to Foundation Medicine between 2012 and 2022. Cases with a potential germline pathogenic variant were identified by filtering single nucleotide variants and short indels by variant allele frequency (VAF) and presence in ClinVar for select cancer susceptibility genes. Odds ratios for AGCT risk were calculated compared to a healthy population. Results: Prior to analysis, 595 patients were screened and 516 with a somatic FOXL2 p.C134W mutation were included. Potential germline pathogenic variants in a DNA repair‐related gene (ATM, BRCA1, BRCA2, CHEK2, PALB2, PMS2, RAD51C, or RAD51D) were found in 6.6% of FOXL2‐mutated AGCT. Potential germline pathogenic CHEK2 variants were found in 3.5% (18/516) of AGCT patients, a rate that was 2.8‐fold higher than Genome Aggregation Database non‐cancer subjects (95% CI 1.8–4.6, p < 0.001). The founder variants p.I157T (38.9%, 7/18) and p.T367fs*15 (c.1100delC; 27.8%, 5/18) were most commonly observed. CHEK2 VAF indicated frequent loss of the wildtype copy of the gene. Conclusions: These results support ongoing utilization of genomic tumor profiling and confirmatory germline testing for potential germline pathogenic variants. Further prospective investigation into the biology of germline variants in this population is warranted. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Orphan nuclear receptor NR2E3 and its small-molecule agonist induce cancer cell apoptosis through regulating p53, IFNα and MYC pathways

Author

Wang, Yidan, primary, Kroll, Todd, additional, Hao, Linhui, additional, Sharma, Ansul, additional, Zhou, Vivian, additional, Moat, Luke, additional, Mayer, John, additional, Shukla, Sanjay S., additional, Hebbring, Scott, additional, Guo, Song, additional, Iden, Marissa, additional, Bissonnette, Adam, additional, Ananiev, Gene, additional, Parashar, Deepak, additional, Rader, Janet S., additional, Janz, Siegfried, additional, and Wen, Zhi, additional

Published
2023
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18. HLA and KIR Associations of Cervical Neoplasia

Author

Bao, Xiao, Hanson, Aimee L., Madeleine, Margaret M., Wang, Sophia S., Schwartz, Stephen M., Newell, Felicity, Pettersson-Kymmer, Ulrika, Hemminki, Kari, Tiews, Sven, Steinberg, Winfried, Rader, Janet S., Castro, Felipe, Safaeian, Mahboobeh, Franco, Eduardo L., Coutlée, François, Ohlsson, Claes, Cortes, Adrian, Marshall, Mhairi, Mukhopadhyay, Pamela, Cremin, Katie, Johnson, Lisa G., Garland, Suzanne M., Tabrizi, Sepehr N., Wentzensen, Nicolas, Sitas, Freddy, Trimble, Cornelia, Little, Julian, Cruickshank, Maggie, Frazer, Ian H., Hildesheim, Allan, Brown, Matthew A., Duncan, Emma L., Sun, YingPu, and Leo, Paul J.

Published
2018

21. Genomic structures and regulation patterns at HPV integration sites in cervical cancer

Author

Porter, Vanessa L., primary, O’Neill, Kieran, additional, MacLennan, Signe, additional, Corbett, Richard D., additional, Ng, Michelle, additional, Culibrk, Luka, additional, Hamadeh, Zeid, additional, Iden, Marissa, additional, Schmidt, Rachel, additional, Tsaih, Shirng-Wern, additional, Chang, Glenn, additional, Fan, Jeremy, additional, Nip, Ka Ming, additional, Akbari, Vahid, additional, Chan, Simon K., additional, Hopkins, James, additional, Moore, Richard A., additional, Chuah, Eric, additional, Mungall, Karen L., additional, Mungall, Andrew J., additional, Birol, Inanc, additional, Jones, Steven J. M., additional, Rader, Janet S., additional, and Marra, Marco A., additional

Published
2023
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23. Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

Author

Caesar-Johnson, Samantha J., Demchok, John A., Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L., Hutter, Carolyn M., Sofia, Heidi J., Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C., Zhang, Jiashan (Julia), Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I., Kim, Jaegil, Lawrence, Michael S., Lin, Pei, Meier, Sam, Noble, Michael S., Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Liu, Yuexin, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M., Hegde, Apurva M., Ju, Zhenlin, Kanchi, Rupa S., Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Mills, Gordon B., Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, Weinstein, John N., Zhang, Jiexin, Abeshouse, Adam, Armenia, Joshua, Chakravarty, Debyani, Chatila, Walid K., de Bruijn, Ino, Gao, Jianjiong, Gross, Benjamin E., Heins, Zachary J., Kundra, Ritika, La, Konnor, Ladanyi, Marc, Luna, Augustin, Nissan, Moriah G., Ochoa, Angelica, Phillips, Sarah M., Reznik, Ed, Sanchez-Vega, Francisco, Sander, Chris, Schultz, Nikolaus, Sheridan, Robert, Sumer, S. Onur, Sun, Yichao, Taylor, Barry S., Wang, Jioajiao, Zhang, Hongxin, Anur, Pavana, Peto, Myron, Spellman, Paul, Benz, Christopher, Stuart, Joshua M., Wong, Christopher K., Yau, Christina, Hayes, D. Neil, Parker, Joel S., Wilkerson, Matthew D., Ally, Adrian, Balasundaram, Miruna, Bowlby, Reanne, Brooks, Denise, Carlsen, Rebecca, Chuah, Eric, Dhalla, Noreen, Holt, Robert, Jones, Steven J.M., Kasaian, Katayoon, Lee, Darlene, Ma, Yussanne, Marra, Marco A., Mayo, Michael, Moore, Richard A., Mungall, Andrew J., Mungall, Karen, Robertson, A. Gordon, Sadeghi, Sara, Schein, Jacqueline E., Sipahimalani, Payal, Tam, Angela, Thiessen, Nina, Tse, Kane, Wong, Tina, Berger, Ashton C., Beroukhim, Rameen, Cherniack, Andrew D., Cibulskis, Carrie, Gabriel, Stacey B., Gao, Galen F., Ha, Gavin, Meyerson, Matthew, Schumacher, Steven E., Shih, Juliann, Kucherlapati, Melanie H., Kucherlapati, Raju S., Baylin, Stephen, Cope, Leslie, Danilova, Ludmila, Bootwalla, Moiz S., Lai, Phillip H., Maglinte, Dennis T., Van Den Berg, David J., Weisenberger, Daniel J., Auman, J. Todd, Balu, Saianand, Bodenheimer, Tom, Fan, Cheng, Hoadley, Katherine A., Hoyle, Alan P., Jefferys, Stuart R., Jones, Corbin D., Meng, Shaowu, Mieczkowski, Piotr A., Mose, Lisle E., Perou, Amy H., Perou, Charles M., Roach, Jeffrey, Shi, Yan, Simons, Janae V., Skelly, Tara, Soloway, Matthew G., Tan, Donghui, Veluvolu, Umadevi, Fan, Huihui, Hinoue, Toshinori, Laird, Peter W., Shen, Hui, Zhou, Wanding, Bellair, Michelle, Chang, Kyle, Covington, Kyle, Creighton, Chad J., Dinh, Huyen, Doddapaneni, HarshaVardhan, Donehower, Lawrence A., Drummond, Jennifer, Gibbs, Richard A., Glenn, Robert, Hale, Walker, Han, Yi, Hu, Jianhong, Korchina, Viktoriya, Lee, Sandra, Lewis, Lora, Li, Wei, Liu, Xiuping, Morgan, Margaret, Morton, Donna, Muzny, Donna, Santibanez, Jireh, Sheth, Margi, Shinbrot, Eve, Wang, Linghua, Wang, Min, Wheeler, David A., Xi, Liu, Zhao, Fengmei, Hess, Julian, Appelbaum, Elizabeth L., Bailey, Matthew, Cordes, Matthew G., Ding, Li, Fronick, Catrina C., Fulton, Lucinda A., Fulton, Robert S., Kandoth, Cyriac, Mardis, Elaine R., McLellan, Michael D., Miller, Christopher A., Schmidt, Heather K., Wilson, Richard K., Crain, Daniel, Curley, Erin, Gardner, Johanna, Lau, Kevin, Mallery, David, Morris, Scott, Paulauskis, Joseph, Penny, Robert, Shelton, Candace, Shelton, Troy, Sherman, Mark, Thompson, Eric, Yena, Peggy, Bowen, Jay, Gastier-Foster, Julie M., Gerken, Mark, Leraas, Kristen M., Lichtenberg, Tara M., Ramirez, Nilsa C., Wise, Lisa, Zmuda, Erik, Corcoran, Niall, Costello, Tony, Hovens, Christopher, Carvalho, Andre L., de Carvalho, Ana C., Fregnani, José H., Longatto-Filho, Adhemar, Reis, Rui M., Scapulatempo-Neto, Cristovam, Silveira, Henrique C.S., Vidal, Daniel O., Burnette, Andrew, Eschbacher, Jennifer, Hermes, Beth, Noss, Ardene, Singh, Rosy, Anderson, Matthew L., Castro, Patricia D., Ittmann, Michael, Huntsman, David, Kohl, Bernard, Le, Xuan, Thorp, Richard, Andry, Chris, Duffy, Elizabeth R., Lyadov, Vladimir, Paklina, Oxana, Setdikova, Galiya, Shabunin, Alexey, Tavobilov, Mikhail, McPherson, Christopher, Warnick, Ronald, Berkowitz, Ross, Cramer, Daniel, Feltmate, Colleen, Horowitz, Neil, Kibel, Adam, Muto, Michael, Raut, Chandrajit P., Malykh, Andrei, Barnholtz-Sloan, Jill S., Barrett, Wendi, Devine, Karen, Fulop, Jordonna, Ostrom, Quinn T., Shimmel, Kristen, Wolinsky, Yingli, Sloan, Andrew E., De Rose, Agostino, Giuliante, Felice, Goodman, Marc, Karlan, Beth Y., Hagedorn, Curt H., Eckman, John, Harr, Jodi, Myers, Jerome, Tucker, Kelinda, Zach, Leigh Anne, Deyarmin, Brenda, Hu, Hai, Kvecher, Leonid, Larson, Caroline, Mural, Richard J., Somiari, Stella, Vicha, Ales, Zelinka, Tomas, Bennett, Joseph, Iacocca, Mary, Rabeno, Brenda, Swanson, Patricia, Latour, Mathieu, Lacombe, Louis, Têtu, Bernard, Bergeron, Alain, McGraw, Mary, Staugaitis, Susan M., Chabot, John, Hibshoosh, Hanina, Sepulveda, Antonia, Su, Tao, Wang, Timothy, Potapova, Olga, Voronina, Olga, Desjardins, Laurence, Mariani, Odette, Roman-Roman, Sergio, Sastre, Xavier, Stern, Marc-Henri, Cheng, Feixiong, Signoretti, Sabina, Berchuck, Andrew, Bigner, Darell, Lipp, Eric, Marks, Jeffrey, McCall, Shannon, McLendon, Roger, Secord, Angeles, Sharp, Alexis, Behera, Madhusmita, Brat, Daniel J., Chen, Amy, Delman, Keith, Force, Seth, Khuri, Fadlo, Magliocca, Kelly, Maithel, Shishir, Olson, Jeffrey J., Owonikoko, Taofeek, Pickens, Alan, Ramalingam, Suresh, Shin, Dong M., Sica, Gabriel, Van Meir, Erwin G., Zhang, Hongzheng, Eijckenboom, Wil, Gillis, Ad, Korpershoek, Esther, Looijenga, Leendert, Oosterhuis, Wolter, Stoop, Hans, van Kessel, Kim E., Zwarthoff, Ellen C., Calatozzolo, Chiara, Cuppini, Lucia, Cuzzubbo, Stefania, DiMeco, Francesco, Finocchiaro, Gaetano, Mattei, Luca, Perin, Alessandro, Pollo, Bianca, Chen, Chu, Houck, John, Lohavanichbutr, Pawadee, Hartmann, Arndt, Stoehr, Christine, Stoehr, Robert, Taubert, Helge, Wach, Sven, Wullich, Bernd, Kycler, Witold, Murawa, Dawid, Wiznerowicz, Maciej, Chung, Ki, Edenfield, W. Jeffrey, Martin, Julie, Baudin, Eric, Bubley, Glenn, Bueno, Raphael, De Rienzo, Assunta, Richards, William G., Kalkanis, Steven, Mikkelsen, Tom, Noushmehr, Houtan, Scarpace, Lisa, Girard, Nicolas, Aymerich, Marta, Campo, Elias, Giné, Eva, Guillermo, Armando López, Van Bang, Nguyen, Hanh, Phan Thi, Phu, Bui Duc, Tang, Yufang, Colman, Howard, Evason, Kimberley, Dottino, Peter R., Martignetti, John A., Gabra, Hani, Juhl, Hartmut, Akeredolu, Teniola, Stepa, Serghei, Hoon, Dave, Ahn, Keunsoo, Kang, Koo Jeong, Beuschlein, Felix, Breggia, Anne, Birrer, Michael, Bell, Debra, Borad, Mitesh, Bryce, Alan H., Castle, Erik, Chandan, Vishal, Cheville, John, Copland, John A., Farnell, Michael, Flotte, Thomas, Giama, Nasra, Ho, Thai, Kendrick, Michael, Kocher, Jean-Pierre, Kopp, Karla, Moser, Catherine, Nagorney, David, O’Brien, Daniel, O’Neill, Brian Patrick, Patel, Tushar, Petersen, Gloria, Que, Florencia, Rivera, Michael, Roberts, Lewis, Smallridge, Robert, Smyrk, Thomas, Stanton, Melissa, Thompson, R. Houston, Torbenson, Michael, Yang, Ju Dong, Zhang, Lizhi, Brimo, Fadi, Ajani, Jaffer A., Gonzalez, Ana Maria Angulo, Behrens, Carmen, Bondaruk, Jolanta, Broaddus, Russell, Czerniak, Bogdan, Esmaeli, Bita, Fujimoto, Junya, Gershenwald, Jeffrey, Guo, Charles, Lazar, Alexander J., Logothetis, Christopher, Meric-Bernstam, Funda, Moran, Cesar, Ramondetta, Lois, Rice, David, Sood, Anil, Tamboli, Pheroze, Thompson, Timothy, Troncoso, Patricia, Tsao, Anne, Wistuba, Ignacio, Carter, Candace, Haydu, Lauren, Hersey, Peter, Jakrot, Valerie, Kakavand, Hojabr, Kefford, Richard, Lee, Kenneth, Long, Georgina, Mann, Graham, Quinn, Michael, Saw, Robyn, Scolyer, Richard, Shannon, Kerwin, Spillane, Andrew, Stretch, onathan, Synott, Maria, Thompson, John, Wilmott, James, Al-Ahmadie, Hikmat, Chan, Timothy A., Ghossein, Ronald, Gopalan, Anuradha, Levine, Douglas A., Reuter, Victor, Singer, Samuel, Singh, Bhuvanesh, Tien, Nguyen Viet, Broudy, Thomas, Mirsaidi, Cyrus, Nair, Praveen, Drwiega, Paul, Miller, Judy, Smith, Jennifer, Zaren, Howard, Park, Joong-Won, Hung, Nguyen Phi, Kebebew, Electron, Linehan, W. Marston, Metwalli, Adam R., Pacak, Karel, Pinto, Peter A., Schiffman, Mark, Schmidt, Laura S., Vocke, Cathy D., Wentzensen, Nicolas, Worrell, Robert, Yang, Hannah, Moncrieff, Marc, Goparaju, Chandra, Melamed, Jonathan, Pass, Harvey, Botnariuc, Natalia, Caraman, Irina, Cernat, Mircea, Chemencedji, Inga, Clipca, Adrian, Doruc, Serghei, Gorincioi, Ghenadie, Mura, Sergiu, Pirtac, Maria, Stancul, Irina, Tcaciuc, Diana, Albert, Monique, Alexopoulou, Iakovina, Arnaout, Angel, Bartlett, John, Engel, Jay, Gilbert, Sebastien, Parfitt, Jeremy, Sekhon, Harman, Thomas, George, Rassl, Doris M., Rintoul, Robert C., Bifulco, Carlo, Tamakawa, Raina, Urba, Walter, Hayward, Nicholas, Timmers, Henri, Antenucci, Anna, Facciolo, Francesco, Grazi, Gianluca, Marino, Mirella, Merola, Roberta, de Krijger, Ronald, Gimenez-Roqueplo, Anne-Paule, Piché, Alain, Chevalier, Simone, McKercher, Ginette, Birsoy, Kivanc, Barnett, Gene, Brewer, Cathy, Farver, Carol, Naska, Theresa, Pennell, Nathan A., Raymond, Daniel, Schilero, Cathy, Smolenski, Kathy, Williams, Felicia, Morrison, Carl, Borgia, Jeffrey A., Liptay, Michael J., Pool, Mark, Seder, Christopher W., Junker, Kerstin, Omberg, Larsson, Dinkin, Mikhail, Manikhas, George, Alvaro, Domenico, Bragazzi, Maria Consiglia, Cardinale, Vincenzo, Carpino, Guido, Gaudio, Eugenio, Chesla, David, Cottingham, Sandra, Dubina, Michael, Moiseenko, Fedor, Dhanasekaran, Renumathy, Becker, Karl-Friedrich, Janssen, Klaus-Peter, Slotta-Huspenina, Julia, Abdel-Rahman, Mohamed H., Aziz, Dina, Bell, Sue, Cebulla, Colleen M., Davis, Amy, Duell, Rebecca, Elder, J. Bradley, Hilty, Joe, Kumar, Bahavna, Lang, James, Lehman, Norman L., Mandt, Randy, Nguyen, Phuong, Pilarski, Robert, Rai, Karan, Schoenfield, Lynn, Senecal, Kelly, Wakely, Paul, Hansen, Paul, Lechan, Ronald, Powers, James, Tischler, Arthur, Grizzle, William E., Sexton, Katherine C., Kastl, Alison, Henderson, Joel, Porten, Sima, Waldmann, Jens, Fassnacht, Martin, Asa, Sylvia L., Schadendorf, Dirk, Couce, Marta, Graefen, Markus, Huland, Hartwig, Sauter, Guido, Schlomm, Thorsten, Simon, Ronald, Tennstedt, Pierre, Olabode, Oluwole, Nelson, Mark, Bathe, Oliver, Carroll, Peter R., Chan, June M., Disaia, Philip, Glenn, Pat, Kelley, Robin K., Landen, Charles N., Phillips, Joanna, Prados, Michael, Simko, Jeffry, Smith-McCune, Karen, VandenBerg, Scott, Roggin, Kevin, Fehrenbach, Ashley, Kendler, Ady, Sifri, Suzanne, Steele, Ruth, Jimeno, Antonio, Carey, Francis, Forgie, Ian, Mannelli, Massimo, Carney, Michael, Hernandez, Brenda, Campos, Benito, Herold-Mende, Christel, Jungk, Christin, Unterberg, Andreas, von Deimling, Andreas, Bossler, Aaron, Galbraith, Joseph, Jacobus, Laura, Knudson, Michael, Knutson, Tina, Ma, Deqin, Milhem, Mohammed, Sigmund, Rita, Godwin, Andrew K., Madan, Rashna, Rosenthal, Howard G., Adebamowo, Clement, Adebamowo, Sally N., Boussioutas, Alex, Beer, David, Giordano, Thomas, Mes-Masson, Anne-Marie, Saad, Fred, Bocklage, Therese, Landrum, Lisa, Mannel, Robert, Moore, Kathleen, Moxley, Katherine, Postier, Russel, Walker, Joan, Zuna, Rosemary, Feldman, Michael, Valdivieso, Federico, Dhir, Rajiv, Luketich, James, Pinero, Edna M. Mora, Quintero-Aguilo, Mario, Carlotti, Carlos Gilberto, Jr., Dos Santos, Jose Sebastião, Kemp, Rafael, Sankarankuty, Ajith, Tirapelli, Daniela, Catto, James, Agnew, Kathy, Swisher, Elizabeth, Creaney, Jenette, Robinson, Bruce, Shelley, Carl Simon, Godwin, Eryn M., Kendall, Sara, Shipman, Cassaundra, Bradford, Carol, Carey, Thomas, Haddad, Andrea, Moyer, Jeffey, Peterson, Lisa, Prince, Mark, Rozek, Laura, Wolf, Gregory, Bowman, Rayleen, Fong, Kwun M., Yang, Ian, Korst, Robert, Rathmell, W. Kimryn, Fantacone-Campbell, J. Leigh, Hooke, Jeffrey A., Kovatich, Albert J., Shriver, Craig D., DiPersio, John, Drake, Bettina, Govindan, Ramaswamy, Heath, Sharon, Ley, Timothy, Van Tine, Brian, Westervelt, Peter, Rubin, Mark A., Lee, Jung Il, Aredes, Natália D., Mariamidze, Armaz, Campbell, Joshua D., Brennan, Kevin, Taylor, Alison M., Wang, Chen, Walter, Vonn, Byers, Lauren Averett, Coarfa, Cristian, Gevaert, Olivier, Prunello, Marcos, Chen, Jianhong, Cheng, Hui, Bullman, Susan, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I., Mungall, Karen L., Schultz, Andre, Gay, Carl M., Hegde, Apurva, Diao, Lixia, Ma, Wencai, Sumazin, Pavel, Chiu, Hua-Sheng, Chen, Ting-Wen, Gunaratne, Preethi, Donehower, Larry, Rader, Janet S., Flores, Elsa R., Tsai, Kenneth Y., Zhou, Jane H., Rustgi, Anil K., Drill, Esther, Shen, Ronglei, Pickering, Curtis R., Chen, Zhong, and Van Waes, Carter

Published
2018
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26. A stratified randomized double-blind phase II trial of celecoxib for treating patients with cervical intraepithelial neoplasia: The potential predictive value of VEGF serum levels: An NRG Oncology/Gynecologic Oncology Group study

Author

Rader, Janet S., Sill, Michael W., Beumer, Jan H., Lankes, Heather A., Benbrook, Doris Mangiaracina, Garcia, Francisco, Trimble, Connie, Tate Thigpen, J., Lieberman, Richard, Zuna, Rosemary E., Leath, Charles A., III, Spirtos, Nick M., Byron, John, Thaker, Premal H., Lele, Shashikant, and Alberts, David

Published
2017
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27. Carboplatin, paclitaxel, and pembrolizumab followed by pembrolizumab maintenance for primary treatment of incompletely resected epithelial ovarian cancer.

Author

Uyar, Denise, Michener, Chad M., Bishop, Erin, Hopp, Elizabeth, Simpson, Pippa, Zhang, Liyun, Rader, Janet S., Rose, Peter G., Mahdi, Haider S., Debernardo, Robert, Christian, Qiana, and Bradley, William

Subjects
OVARIAN epithelial cancer, PEMBROLIZUMAB, IMMUNE checkpoint inhibitors, PACLITAXEL, CARBOPLATIN, PROGRESSION-free survival
Abstract

Objective: Incompletely resected epithelial ovarian cancer represents a poor prognostic subset of patients. Novel treatment strategies are needed to improve outcomes for this population. We evaluated a treatment strategy combining platinum-based chemotherapy with pembrolizumab followed by pembrolizumab maintenance therapy in the first-line treatment after incomplete resection of epithelial ovarian cancer patients. Methods: This was a single-arm, non-randomized pilot study of carboplatin, taxane, and immune checkpoint inhibitor, pembrolizumab, followed by 12 months of maintenance pembrolizumab in patients with incompletely resected epithelial ovarian cancer (EOC). Results: A total of 29 patients were enrolled and evaluated for efficacy and safety. The best response to therapy was complete response in 16 (55%) patients, partial response in 9 (31%) patients, and 3 (10%) patients with progression of disease. The median progression-free survival (PFS) was 13.2 months. Grade 3 and 4 toxicities occurred in 20% of patients. In all, 7 patients discontinued therapy due to adverse events. Quality-of-life scores remained high during therapy. Response to therapy did not correlate with PD-L1 tumor expression. Conclusions: Combination platinum--taxane therapy with pembrolizumab did not increase median progression-free survival in this cohort of patients. Key message: EOC is an immunogenic disease, but immune checkpoint inhibitor therapy has yet to impact outcomes. The current study utilized pembrolizumab in combination with standard chemotherapy followed by a maintenance treatment strategy in incompletely resected EOC. Progression-free survival was not extended in this poor prognostic group with combined chemotherapy and immunotherapy. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Supplementary Data from Oncostatin M Receptor–Targeted Antibodies Suppress STAT3 Signaling and Inhibit Ovarian Cancer Growth

Author

Geethadevi, Anjali, primary, Nair, Ajay, primary, Parashar, Deepak, primary, Ku, Zhiqiang, primary, Xiong, Wei, primary, Deng, Hui, primary, Li, Yongsheng, primary, George, Jasmine, primary, McAllister, Donna M., primary, Sun, Yunguang, primary, Kadamberi, Ishaque P., primary, Gupta, Prachi, primary, Dwinell, Michael B., primary, Bradley, William H., primary, Rader, Janet S., primary, Rui, Hallgeir, primary, Schwabe, Robert F., primary, Zhang, Ningyan, primary, Pradeep, Sunila, primary, An, Zhiqiang, primary, and Chaluvally-Raghavan, Pradeep, primary

Published
2023
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31. Data from Oncostatin M Receptor–Targeted Antibodies Suppress STAT3 Signaling and Inhibit Ovarian Cancer Growth

Author

Geethadevi, Anjali, primary, Nair, Ajay, primary, Parashar, Deepak, primary, Ku, Zhiqiang, primary, Xiong, Wei, primary, Deng, Hui, primary, Li, Yongsheng, primary, George, Jasmine, primary, McAllister, Donna M., primary, Sun, Yunguang, primary, Kadamberi, Ishaque P., primary, Gupta, Prachi, primary, Dwinell, Michael B., primary, Bradley, William H., primary, Rader, Janet S., primary, Rui, Hallgeir, primary, Schwabe, Robert F., primary, Zhang, Ningyan, primary, Pradeep, Sunila, primary, An, Zhiqiang, primary, and Chaluvally-Raghavan, Pradeep, primary

Published
2023
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32. Supplementary Spread Sheet 1 from Peritoneal Spread of Ovarian Cancer Harbors Therapeutic Vulnerabilities Regulated by FOXM1 and EGFR/ERBB2 Signaling

Author

Parashar, Deepak, primary, Nair, Bindu, primary, Geethadevi, Anjali, primary, George, Jasmine, primary, Nair, Ajay, primary, Tsaih, Shirng-Wern, primary, Kadamberi, Ishaque P., primary, Gopinadhan Nair, Gopa Kumar, primary, Lu, Yiling, primary, Ramchandran, Ramani, primary, Uyar, Denise S., primary, Rader, Janet S., primary, Ram, Prahlad T., primary, Mills, Gordon B., primary, Pradeep, Sunila, primary, and Chaluvally-Raghavan, Pradeep, primary

Published
2023
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34. Supplementary Spread Sheet 2 from Peritoneal Spread of Ovarian Cancer Harbors Therapeutic Vulnerabilities Regulated by FOXM1 and EGFR/ERBB2 Signaling

Author

Parashar, Deepak, primary, Nair, Bindu, primary, Geethadevi, Anjali, primary, George, Jasmine, primary, Nair, Ajay, primary, Tsaih, Shirng-Wern, primary, Kadamberi, Ishaque P., primary, Gopinadhan Nair, Gopa Kumar, primary, Lu, Yiling, primary, Ramchandran, Ramani, primary, Uyar, Denise S., primary, Rader, Janet S., primary, Ram, Prahlad T., primary, Mills, Gordon B., primary, Pradeep, Sunila, primary, and Chaluvally-Raghavan, Pradeep, primary

Published
2023
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37. Combined Supplementary Materials from Peritoneal Spread of Ovarian Cancer Harbors Therapeutic Vulnerabilities Regulated by FOXM1 and EGFR/ERBB2 Signaling

Author

Parashar, Deepak, primary, Nair, Bindu, primary, Geethadevi, Anjali, primary, George, Jasmine, primary, Nair, Ajay, primary, Tsaih, Shirng-Wern, primary, Kadamberi, Ishaque P., primary, Gopinadhan Nair, Gopa Kumar, primary, Lu, Yiling, primary, Ramchandran, Ramani, primary, Uyar, Denise S., primary, Rader, Janet S., primary, Ram, Prahlad T., primary, Mills, Gordon B., primary, Pradeep, Sunila, primary, and Chaluvally-Raghavan, Pradeep, primary

Published
2023
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39. Data from Peritoneal Spread of Ovarian Cancer Harbors Therapeutic Vulnerabilities Regulated by FOXM1 and EGFR/ERBB2 Signaling

Author

Parashar, Deepak, primary, Nair, Bindu, primary, Geethadevi, Anjali, primary, George, Jasmine, primary, Nair, Ajay, primary, Tsaih, Shirng-Wern, primary, Kadamberi, Ishaque P., primary, Gopinadhan Nair, Gopa Kumar, primary, Lu, Yiling, primary, Ramchandran, Ramani, primary, Uyar, Denise S., primary, Rader, Janet S., primary, Ram, Prahlad T., primary, Mills, Gordon B., primary, Pradeep, Sunila, primary, and Chaluvally-Raghavan, Pradeep, primary

Published
2023
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40. Combined Supplementary Data from Oncostatin M Receptor–Targeted Antibodies Suppress STAT3 Signaling and Inhibit Ovarian Cancer Growth

Author

Geethadevi, Anjali, primary, Nair, Ajay, primary, Parashar, Deepak, primary, Ku, Zhiqiang, primary, Xiong, Wei, primary, Deng, Hui, primary, Li, Yongsheng, primary, George, Jasmine, primary, McAllister, Donna M., primary, Sun, Yunguang, primary, Kadamberi, Ishaque P., primary, Gupta, Prachi, primary, Dwinell, Michael B., primary, Bradley, William H., primary, Rader, Janet S., primary, Rui, Hallgeir, primary, Schwabe, Robert F., primary, Zhang, Ningyan, primary, Pradeep, Sunila, primary, An, Zhiqiang, primary, and Chaluvally-Raghavan, Pradeep, primary

Published
2023
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42. SupplementaryMethods.docx from Oncostatin M Receptor–Targeted Antibodies Suppress STAT3 Signaling and Inhibit Ovarian Cancer Growth

Author

Geethadevi, Anjali, primary, Nair, Ajay, primary, Parashar, Deepak, primary, Ku, Zhiqiang, primary, Xiong, Wei, primary, Deng, Hui, primary, Li, Yongsheng, primary, George, Jasmine, primary, McAllister, Donna M., primary, Sun, Yunguang, primary, Kadamberi, Ishaque P., primary, Gupta, Prachi, primary, Dwinell, Michael B., primary, Bradley, William H., primary, Rader, Janet S., primary, Rui, Hallgeir, primary, Schwabe, Robert F., primary, Zhang, Ningyan, primary, Pradeep, Sunila, primary, An, Zhiqiang, primary, and Chaluvally-Raghavan, Pradeep, primary

Published
2023
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44. Supplementary Figure S6. Sensitivity and specificity of methylation as a quantitative classifier of cervical precancer and cancer samples from Targeted, Deep Sequencing Reveals Full Methylation Profiles of Multiple HPV Types and Potential Biomarkers for Cervical Cancer Progression

Author

Liu, Pengyuan, primary, Iden, Marissa, primary, Fye, Samantha, primary, Huang, Yi-Wen, primary, Hopp, Elizabeth, primary, Chu, Chen, primary, Lu, Yan, primary, and Rader, Janet S., primary

Published
2023
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47. Supplementary Tables 1-2, Methods and Figures 1-2 from Profiling Microdissected Epithelium and Stroma to Model Genomic Signatures for Cervical Carcinogenesis Accommodating for Covariates

Author

Gius, David, primary, Funk, Margo C., primary, Chuang, Eric Y., primary, Feng, Sheng, primary, Huettner, Phyllis C., primary, Nguyen, Loan, primary, Bradbury, C. Matthew, primary, Mishra, Mark, primary, Gao, Shuping, primary, Buttin, Barbara M., primary, Cohn, David E., primary, Powell, Matthew A., primary, Horowitz, Neil S., primary, Whitcomb, Bradford P., primary, and Rader, Janet S., primary

Published
2023
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50. Data from Profiling Microdissected Epithelium and Stroma to Model Genomic Signatures for Cervical Carcinogenesis Accommodating for Covariates

Author

Gius, David, primary, Funk, Margo C., primary, Chuang, Eric Y., primary, Feng, Sheng, primary, Huettner, Phyllis C., primary, Nguyen, Loan, primary, Bradbury, C. Matthew, primary, Mishra, Mark, primary, Gao, Shuping, primary, Buttin, Barbara M., primary, Cohn, David E., primary, Powell, Matthew A., primary, Horowitz, Neil S., primary, Whitcomb, Bradford P., primary, and Rader, Janet S., primary

Published
2023
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