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Your search keyword '"Ma, Yussanne"' showing total 11 results
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11 results on '"Ma, Yussanne"'

1. 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, Sexually Transmitted Infections, Cancer, Genetics, Cervical Cancer, Human Genome, HIV/AIDS, Infectious Diseases, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Infection, Biological Sciences, Medical and Health Sciences, Developmental Biology
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

2. Comparative RNA-Sequencing Analysis Benefits a Pediatric Patient With Relapsed Cancer

Author

Newton, Yulia, Rassekh, S Rod, Deyell, Rebecca J, Shen, Yaoqing, Jones, Martin R, Dunham, Chris, Yip, Stephen, Leelakumari, Sreeja, Zhu, Jingchun, McColl, Duncan, Swatloski, Teresa, Salama, Sofie R, Ng, Tony, Hendson, Glenda, Lee, Anna F, Ma, Yussanne, Moore, Richard, Mungall, Andrew J, Haussler, David, Stuart, Joshua M, Jantzen, Colleen, Laskin, Janessa, Jones, Steven JM, Marra, Marco A, and Morozova, Olena

Subjects
Genetics, Pediatric Research Initiative, Pediatric, Biotechnology, Pediatric Cancer, Human Genome, Rare Diseases, Cancer, Oncology and carcinogenesis
Abstract

Clinical detection of sequence and structural variants in known cancer genes points to viable treatment options for a minority of children with cancer.1 To increase the number of children who benefit from genomic profiling, gene expression information must be considered alongside mutations.2,3 Although high expression has been used to nominate drug targets for pediatric cancers,4,5 its utility has not been evaluated in a systematic way.6 We describe a child with a rare sarcoma that was profiled with whole-genome and RNA sequencing (RNA-Seq) techniques. Although the tumor did not harbor DNA mutations targetable by available therapies, incorporation of gene expression information derived from RNA-Seq analysis led to a therapy that produced a significant clinical response. We use this case to describe a framework for inclusion of gene expression into the clinical genomic evaluation of pediatric tumors.

Published
2018

3. The Integrated Genomic Landscape of Thymic Epithelial Tumors

Author

Radovich, Milan, Pickering, Curtis R, Felau, Ina, Ha, Gavin, Zhang, Hailei, Jo, Heejoon, Hoadley, Katherine A, Anur, Pavana, Zhang, Jiexin, McLellan, Mike, Bowlby, Reanne, Matthew, Thomas, Danilova, Ludmila, Hegde, Apurva M, Kim, Jaegil, Leiserson, Mark DM, Sethi, Geetika, Lu, Charles, Ryan, Michael, Su, Xiaoping, Cherniack, Andrew D, Robertson, Gordon, Akbani, Rehan, Spellman, Paul, Weinstein, John N, Hayes, D Neil, Raphael, Ben, Lichtenberg, Tara, Leraas, Kristen, Zenklusen, Jean Claude, Network, The Cancer Genome Atlas, Ally, Adrian, Appelbaum, Elizabeth L, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Behera, Madhusmita, Beroukhim, Rameen, Berrios, Mario, Blandino, Giovanni, Bodenheimer, Tom, Bootwalla, Moiz S, Bowen, Jay, Brooks, Denise, Carcano, Flavio M, Carlsen, Rebecca, Carvalho, Andre L, Castro, Patricia, Chalabreysse, Lara, Chin, Lynda, Cho, Juok, Choe, Gina, Chuah, Eric, Chudamani, Sudha, Cibulskis, Carrie, Cope, Leslie, Cordes, Matthew G, Crain, Daniel, Curley, Erin, Defreitas, Timothy, Demchok, John A, Detterbeck, Frank, Dhalla, Noreen, Dienemann, Hendrik, Edenfield, W Jeff, Facciolo, Francesco, Ferguson, Martin L, Frazer, Scott, Fronick, Catrina C, Fulton, Lucinda A, Fulton, Robert S, Gabriel, Stacey B, Gardner, Johanna, Gastier-Foster, Julie M, Gehlenborg, Nils, Gerken, Mark, Getz, Gad, Heiman, David I, Hobensack, Shital, Holbrook, Andrea, Holt, Robert A, Hoyle, Alan P, Hutter, Carolyn M, Ittmann, Michael, Jefferys, Stuart R, Jones, Corbin D, Jones, Steven JM, Kasaian, Katayoon, Kimes, Patrick K, Lai, Phillip H, Laird, Peter W, Lawrence, Michael S, Lin, Pei, Liu, Jia, Lolla, Laxmi, Lu, Yiling, Ma, Yussanne, Maglinte, Dennis T, and Mallery, David

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Human Genome, Autoimmune Disease, Cancer, Rare Diseases, Biotechnology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Adolescent, Adult, Aged, Aged, 80 and over, Female, Genomics, Humans, Male, Middle Aged, Mutation, Neoplasms, Glandular and Epithelial, Thymoma, Thymus Neoplasms, Transcription Factors, TFII, Young Adult, Cancer Genome Atlas Network, TCGA, autoimmunity, genomics, myasthenia gravis, proteomics, thymic carcinoma, thymic epithelial tumors, thymoma, transcriptomics, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Thymic epithelial tumors (TETs) are one of the rarest adult malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with autoimmune diseases, followed by thymic carcinoma, which is less common but more clinically aggressive. Using multi-platform omics analyses on 117 TETs, we define four subtypes of these tumors defined by genomic hallmarks and an association with survival and World Health Organization histological subtype. We further demonstrate a marked prevalence of a thymoma-specific mutated oncogene, GTF2I, and explore its biological effects on multi-platform analysis. We further observe enrichment of mutations in HRAS, NRAS, and TP53. Last, we identify a molecular link between thymoma and the autoimmune disease myasthenia gravis, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy.

Published
2018

4. The whole-genome landscape of medulloblastoma subtypes

Author

Northcott, Paul A, Buchhalter, Ivo, Morrissy, A Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Ehrenberger, Tobias, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A, Warnatz, Hans-Jörg, Sidiropoulos, Nikos, Phillips, Aaron H, Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M, Erkek, Serap, Jones, David TW, Worst, Barbara C, Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D, Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D, Wolf, Stephan, Robinson, Giles W, Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence MG, Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon-Jae, Pomeroy, Scott L, Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M, Mora, Jaume, McLendon, Roger E, Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A, Mungall, Andrew J, Mungall, Karen L, Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven JM, Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie-Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Fraenkel, Ernest, Korbel, Jan O, Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A, Pfister, Stefan M, Taylor, Michael D, and Lichter, Peter

Subjects
Cancer, Human Genome, Brain Disorders, Pediatric Cancer, Brain Cancer, Genetics, Biotechnology, Rare Diseases, Neurosciences, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Good Health and Well Being, Carcinogenesis, Carrier Proteins, Cohort Studies, DNA Methylation, DNA Mutational Analysis, Datasets as Topic, Epistasis, Genetic, Genome, Human, Genomics, Humans, Medulloblastoma, Molecular Targeted Therapy, Muscle Proteins, Mutation, Oncogenes, Transcription Factors, Whole Genome Sequencing, Wnt Proteins, General Science & Technology
Abstract

Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.

Published
2017

5. Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma

Author

Ally, Adrian, Balasundaram, Miruna, Carlsen, Rebecca, Chuah, Eric, Clarke, Amanda, Dhalla, Noreen, Holt, Robert A, Jones, Steven JM, Lee, Darlene, Ma, Yussanne, Marra, Marco A, Mayo, Michael, Moore, Richard A, Mungall, Andrew J, Schein, Jacqueline E, Sipahimalani, Payal, Tam, Angela, Thiessen, Nina, Cheung, Dorothy, Wong, Tina, Brooks, Denise, Robertson, A Gordon, Bowlby, Reanne, Mungall, Karen, Sadeghi, Sara, Xi, Liu, Covington, Kyle, Shinbrot, Eve, Wheeler, David A, Gibbs, Richard A, Donehower, Lawrence A, Wang, Linghua, Bowen, Jay, Gastier-Foster, Julie M, Gerken, Mark, Helsel, Carmen, Leraas, Kristen M, Lichtenberg, Tara M, Ramirez, Nilsa C, Wise, Lisa, Zmuda, Erik, Gabriel, Stacey B, Meyerson, Matthew, Cibulskis, Carrie, Murray, Bradley A, Shih, Juliann, Beroukhim, Rameen, Cherniack, Andrew D, Schumacher, Steven E, Saksena, Gordon, Pedamallu, Chandra Sekhar, Chin, Lynda, Getz, Gad, Noble, Michael, Zhang, Hailei, Heiman, David, Cho, Juok, Gehlenborg, Nils, Voet, Douglas, Lin, Pei, Frazer, Scott, Defreitas, Timothy, Meier, Sam, Lawrence, Michael, Kim, Jaegil, Creighton, Chad J, Muzny, Donna, Doddapaneni, HarshaVardhan, Hu, Jianhong, Wang, Min, Morton, Donna, Korchina, Viktoriya, Han, Yi, Dinh, Huyen, Lewis, Lora, Bellair, Michelle, Liu, Xiuping, Santibanez, Jireh, Glenn, Robert, Lee, Sandra, Hale, Walker, Parker, Joel S, Wilkerson, Matthew D, Hayes, D Neil, Reynolds, Sheila M, Shmulevich, Ilya, Zhang, Wei, Liu, Yuexin, Iype, Lisa, Makhlouf, Hala, Torbenson, Michael S, Kakar, Sanjay, Yeh, Matthew M, Jain, Dhanpat, Kleiner, David E, Dhanasekaran, Renumathy, El-Serag, Hashem B, and Yim, Sun Young

Subjects
Human Genome, Digestive Diseases, Biotechnology, Rare Diseases, Genetics, Liver Disease, Liver Cancer, Cancer, Aetiology, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, Carcinoma, Hepatocellular, DNA Methylation, Genomics, Humans, Isocitrate Dehydrogenase, Liver Neoplasms, MicroRNAs, Mutation, Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu, Cancer Genome Atlas Research Network, IDH1/2, TP53, cancer subtyping, expression profile, hepatocellular carcinoma, metabolic reprogramming, promoter hypermethylation, significantly mutated genes, sonic hedgehog signaling, stem cell phenotype, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing and DNA copy number analyses, and we analyzed 196 HCC cases by DNA methylation, RNA, miRNA, and proteomic expression also. DNA sequencing and mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or downregulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed. Integrative molecular HCC subtyping incorporating unsupervised clustering of five data platforms identified three subtypes, one of which was associated with poorer prognosis in three HCC cohorts. Integrated analyses enabled development of a p53 target gene expression signature correlating with poor survival. Potential therapeutic targets for which inhibitors exist include WNT signaling, MDM4, MET, VEGFA, MCL1, IDH1, TERT, and immune checkpoint proteins CTLA-4, PD-1, and PD-L1.

Published
2017

6. Integrated Molecular Characterization of Uterine Carcinosarcoma

Author

Cherniack, Andrew D, Shen, Hui, Walter, Vonn, Stewart, Chip, Murray, Bradley A, Bowlby, Reanne, Hu, Xin, Ling, Shiyun, Soslow, Robert A, Broaddus, Russell R, Zuna, Rosemary E, Robertson, Gordon, Laird, Peter W, Kucherlapati, Raju, Mills, Gordon B, Network, The Cancer Genome Atlas Research, Akbani, Rehan, Ally, Adrian, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Baylin, Stephen B, Beroukhim, Rameen, Bodenheimer, Tom, Bogomolniy, Faina, Boice, Lori, Bootwalla, Moiz S, Bowen, Jay, Broaddus, Russell, Brooks, Denise, Carlsen, Rebecca, Cho, Juok, Chuah, Eric, Chudamani, Sudha, Cibulskis, Kristian, Cline, Melissa, Dao, Fanny, David, Mutch, Demchok, John A, Dhalla, Noreen, Dowdy, Sean, Felau, Ina, Ferguson, Martin L, Frazer, Scott, Frick, Jessica, Gabriel, Stacey, Gastier-Foster, Julie M, Gehlenborg, Nils, Gerken, Mark, Getz, Gad, Gupta, Manaswi, Haussler, David, Hayes, D Neil, Heiman, David I, Hess, Julian, Hoadley, Katherine A, Hoffmann, Robert, Holt, Robert A, Hoyle, Alan P, Huang, Mei, Hutter, Carolyn M, Jefferys, Stuart R, Jones, Steven JM, Jones, Corbin D, Kanchi, Rupa S, Kandoth, Cyriac, Kasaian, Katayoon, Kerr, Sarah, Kim, Jaegil, Lai, Phillip H, Lander, Eric, Lawrence, Michael S, Lee, Darlene, Leraas, Kristen M, Leshchiner, Ignaty, Levine, Douglas A, Lichtenberg, Tara M, Lin, Pei, Liu, Jia, Liu, Wenbin, Liu, Yuexin, Lolla, Laxmi, Lu, Yiling, Ma, Yussanne, Maglinte, Dennis T, Marra, Marco A, Mayo, Michael, Meng, Shaowu, Meyerson, Matthew, Mieczkowski, Piotr A, Moore, Richard A, Mose, Lisle E, Mungall, Andrew J, and Mungall, Karen

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Reproductive Medicine, Human Genome, Cancer, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Carcinosarcoma, DNA Copy Number Variations, Epithelial-Mesenchymal Transition, Female, Humans, Mutation, Uterine Neoplasms, Cancer Genome Atlas Research Network, EMT, TGGA, The Cancer Genome Atlas, UCS, endometrial cancer, epithelial-to-mesenchymal transition, gynecologic cancer, gynecologic oncology, translational science, uterine carcinosarcoma, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified.

Published
2017

7. 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

8. Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

Author

Zheng, Siyuan, Cherniack, Andrew D, Dewal, Ninad, Moffitt, Richard A, Danilova, Ludmila, Murray, Bradley A, Lerario, Antonio M, Else, Tobias, Knijnenburg, Theo A, Ciriello, Giovanni, Kim, Seungchan, Assie, Guillaume, Morozova, Olena, Akbani, Rehan, Shih, Juliann, Hoadley, Katherine A, Choueiri, Toni K, Waldmann, Jens, Mete, Ozgur, Robertson, A Gordon, Wu, Hsin-Ta, Raphael, Benjamin J, Shao, Lina, Meyerson, Matthew, Demeure, Michael J, Beuschlein, Felix, Gill, Anthony J, Sidhu, Stan B, Almeida, Madson Q, Fragoso, Maria CBV, Cope, Leslie M, Kebebew, Electron, Habra, Mouhammed A, Whitsett, Timothy G, Bussey, Kimberly J, Rainey, William E, L., Sylvia, Bertherat, Jérôme, Fassnacht, Martin, Wheeler, David A, Network, The Cancer Genome Atlas Research, Verhaak, Roel GW, Giordano, Thomas J, Hammer, Gary D, Assié, Guillaume, Wu, Hsin-Tu, Almeida, Madson, Fragoso, Maria Candida Barisson, Habra, Mouhammed Amir, Benz, Christopher, Ally, Adrian, Balasundaram, Miruna, Bowlby, Reanne, Brooks, Denise, Butterfield, Yaron SN, Carlsen, Rebecca, Dhalla, Noreen, Guin, Ranabir, Holt, Robert A, Jones, Steven JM, Kasaian, Katayoon, Lee, Darlene, Li, Haiyan I, Lim, Lynette, Ma, Yussanne, and Marra, Marco A

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Human Genome, Cancer, Rare Diseases, Biotechnology, Clinical Research, Adolescent, Adrenal Cortex Neoplasms, Adrenocortical Carcinoma, Adult, Aged, Aged, 80 and over, Child, DNA Methylation, Disease-Free Survival, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, Genome, Human, Genomics, Humans, Male, Middle Aged, Mutation, Outcome Assessment, Health Care, Prognosis, Young Adult, Cancer Genome Atlas Research Network, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

We describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers.

Published
2016

9. Comprehensive molecular characterization of gastric adenocarcinoma

Author

Bass, Adam J, Thorsson, Vesteinn, Shmulevich, Ilya, Reynolds, Sheila M, Miller, Michael, Bernard, Brady, Hinoue, Toshinori, Laird, Peter W, Curtis, Christina, Shen, Hui, Weisenberger, Daniel J, Schultz, Nikolaus, Shen, Ronglai, Weinhold, Nils, Kelsen, David P, Bowlby, Reanne, Chu, Andy, Kasaian, Katayoon, Mungall, Andrew J, Robertson, A Gordon, Sipahimalani, Payal, Cherniack, Andrew, Getz, Gad, Liu, Yingchun, Noble, Michael S, Pedamallu, Chandra, Sougnez, Carrie, Taylor-Weiner, Amaro, Akbani, Rehan, Lee, Ju-Seog, Liu, Wenbin, Mills, Gordon B, Yang, Da, Zhang, Wei, Pantazi, Angeliki, Parfenov, Michael, Gulley, Margaret, Piazuelo, M Blanca, Schneider, Barbara G, Kim, Jihun, Boussioutas, Alex, Sheth, Margi, Demchok, John A, Rabkin, Charles S, Willis, Joseph E, Ng, Sam, Garman, Katherine, Beer, David G, Pennathur, Arjun, Raphael, Benjamin J, Wu, Hsin-Ta, Odze, Robert, Kim, Hark K, Bowen, Jay, Leraas, Kristen M, Lichtenberg, Tara M, Weaver, Stephanie, McLellan, Michael, Wiznerowicz, Maciej, Sakai, Ryo, Lawrence, Michael S, Cibulskis, Kristian, Lichtenstein, Lee, Fisher, Sheila, Gabriel, Stacey B, Lander, Eric S, Ding, Li, Niu, Beifang, Ally, Adrian, Balasundaram, Miruna, Birol, Inanc, Brooks, Denise, Butterfield, Yaron SN, Carlsen, Rebecca, Chu, Justin, Chuah, Eric, Chun, Hye-Jung E, Clarke, Amanda, Dhalla, Noreen, Guin, Ranabir, Holt, Robert A, Jones, Steven JM, Lee, Darlene, Li, Haiyan A, Lim, Emilia, Ma, Yussanne, Marra, Marco A, Mayo, Michael, Moore, Richard A, Mungall, Karen L, Ming Nip, Ka, and Schein, Jacqueline E

Subjects
Genetics, Digestive Diseases, Genetic Testing, Human Genome, Rare Diseases, Cancer, Good Health and Well Being, Adenocarcinoma, Female, Gene Expression Regulation, Neoplastic, Genome, Human, Herpesvirus 4, Human, Humans, Male, Mutation, Proteome, Stomach Neoplasms, Cancer Genome Atlas Research Network, General Science & Technology
Abstract

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.

Published
2014

10. Genomic and Cytogenetic Characterization of a Balanced Translocation Disrupting NUP98.

Author

Thibodeau, My Linh, Steinraths, Michelle, Brown, Lindsay, Zong, Zheyuan, Shomer, Naomi, Taubert, Stefan, Mungall, Karen L., Ma, Yussanne P., Mueller, Rosemary, Birol, Inanc, and Lehman, anna

Subjects
GENOMICS, TUBEROUS sclerosis, GENETIC testing, GENES, HUMAN genome
Abstract

A 41-year-old Asian woman with bilateral renal angiomyolipomas (AML) was incidentally identified to have a balanced translocation, 46,XX,t(11; 12)(p15.4;q 15). She had no other features or family history to suggest a diagnosis of tuberous sclerosis. Her healthy daughter had the same translocation and no renal AML at the age of 3 years. Whole-genome sequencing was performed on genomic maternal DNA isolated from blood. A targeted de novo assembly was then conducted with ABySS for chromosomes 11 and 12. Sanger sequencing was used to validate the translocation breakpoints. As a result, genomic characterization of chromosomes 11 and 12 revealed that the 11 p breakpoint disrupted the NUP98 gene in intron 1, causing a separation of the promoter and transcription start site from the rest of the gene. The translocation breakpoint on chromosome 12q was located in a gene desert. NUP98 has not yet been associated with renal AML pathogenesis, but somatic NUP98 alterations are recurrently implicated in hematological malignancies, most often following a gene fusion event. We also found evidence for complex structural events involving chromosome 12, which appear to disrupt the TDG gene. We identified a TDGP1 partially processed pseudogene at 12p 12.1, which adds complexity to the de novo assembly. In conclusion, this is the first report of a germline constitutional structural chromosome rearrangement disrupting NUP98 that occurred in a generally healthy woman with bilateral renal AML. [ABSTRACT FROM AUTHOR]

Published
2017
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11. Integrative genomic analysis of ghost cell odontogenic carcinoma.

Author

Bose, Pinaki, Pleasance, Erin D., Jones, Martin, Shen, Yaoqing, Ch’ng, Carolyn, Reisle, Caralyn, Schein, Jacqueline E., Mungall, Andrew J., Moore, Richard, Ma, Yussanne, Sheffield, Brandon S., Thomson, Thomas, Rasmussen, Steven, Ng, Tony, Yip, Stephen, Lee, Christopher W., Ho, Cheryl, Laskin, Janessa, Marra, Marco A., and Jones, Steven J.

Subjects
*ODONTOGENIC tumors, *HUMAN genome, *INTEGRATIVE oncology, *MEDICAL research, *PATIENTS, *TUMOR treatment
Published
2015
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