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1. Single-cell stabilization method identifies gonadotrope transcriptional dynamics and pituitary cell type heterogeneity

Author

Ruf-Zamojski, Frederique, Ge, Yongchao, Nair, Venugopalan, Zamojski, Michel, Pincas, Hanna, Toufaily, Chirine, Tome-Garcia, Jessica, Stoeckius, Marlon, Stephenson, William, Smith, Gregory R, Bernard, Daniel J, Tsankova, Nadejda M, Hartmann, Boris M, Fribourg, Miguel, Smibert, Peter, Swerdlow, Harold, Turgeon, Judith L, and Sealfon, Stuart C

Subjects
Biotechnology, Genetics, Contraception/Reproduction, Underpinning research, 1.1 Normal biological development and functioning, Animals, Buffers, Cell Line, Tumor, Dose-Response Relationship, Drug, Early Growth Response Protein 1, Early Growth Response Protein 2, Genes, Immediate-Early, Genetic Heterogeneity, Gonadotrophs, Gonadotropin-Releasing Hormone, Mice, Proto-Oncogene Proteins c-fos, RNA Stability, RNA, Messenger, Sequence Analysis, RNA, Single-Cell Analysis, Transcriptional Activation, Transcriptome, Environmental Sciences, Biological Sciences, Information and Computing Sciences, Developmental Biology
Abstract

Immediate-early response genes (IEGs) are rapidly and transiently induced following an extracellular signal. Elucidating the IEG response patterns in single cells (SCs) requires assaying large numbers of timed samples at high accuracy while minimizing handling effects. To achieve this, we developed and validated RNA stabilization Buffer for Examination of Single-cell Transcriptomes (RNA-Best), a versatile single-step cell and tissue preservation protocol that stabilizes RNA in intact SCs without perturbing transcription patterns. We characterize for the first time SC heterogeneity in IEG responses to pulsatile gonadotropin-releasing hormone (GnRH) stimuli in pituitary gonadotrope cells. Our study identifies a gene-specific hierarchical pattern of all-or-none transcript induction elicited by increasing concentrations of GnRH. This quantal pattern of gene activation raises the possibility that IEG activation, when accurately resolved at the SC level, may be mediated by gene bits that behave as pure binary switches.

Published
2018

2. International network of cancer genome projects

Author

Hudson (Chairperson), Thomas J, Anderson, Warwick, Aretz, Axel, Barker, Anna D, Bell, Cindy, Bernabé, Rosa R, Bhan, MK, Calvo, Fabien, Eerola, Iiro, Gerhard, Daniela S, Guttmacher, Alan, Guyer, Mark, Hemsley, Fiona M, Jennings, Jennifer L, Kerr, David, Klatt, Peter, Kolar, Patrik, Kusuda, Jun, Lane, David P, Laplace, Frank, Lu, Youyong, Nettekoven, Gerd, Ozenberger, Brad, Peterson, Jane, Rao, TS, Remacle, Jacques, Schafer, Alan J, Shibata, Tatsuhiro, Stratton, Michael R, Vockley, Joseph G, Watanabe, Koichi, Yang, Huanming, Yuen, Matthew MF, Knoppers (Leader), Bartha M, Bobrow, Martin, Cambon-Thomsen, Anne, Dressler, Lynn G, Dyke, Stephanie OM, Joly, Yann, Kato, Kazuto, Kennedy, Karen L, Nicolás, Pilar, Parker, Michael J, Rial-Sebbag, Emmanuelle, Romeo-Casabona, Carlos M, Shaw, Kenna M, Wallace, Susan, Wiesner, Georgia L, Zeps, Nikolajs, Lichter (Leader), Peter, Biankin, Andrew V, Chabannon, Christian, Chin, Lynda, Clément, Bruno, de Alava, Enrique, Degos, Françoise, Ferguson, Martin L, Geary, Peter, Hayes, D Neil, Hudson, Thomas J, Johns, Amber L, Kasprzyk, Arek, Nakagawa, Hidewaki, Penny, Robert, Piris, Miguel A, Sarin, Rajiv, Scarpa, Aldo, van de Vijver, Marc, Futreal (Leader), P Andrew, Aburatani, Hiroyuki, Bayés, Mónica, Bowtell, David DL, Campbell, Peter J, Estivill, Xavier, Grimmond, Sean M, Gut, Ivo, Hirst, Martin, López-Otín, Carlos, Majumder, Partha, Marra, Marco, McPherson, John D, Ning, Zemin, Puente, Xose S, Ruan, Yijun, Stunnenberg, Hendrik G, Swerdlow, Harold, Velculescu, Victor E, Wilson, Richard K, Xue, Hong H, Yang, Liu, Spellman (Leader), Paul T, Bader, Gary D, Boutros, Paul C, and Flicek, Paul

Subjects
Cancer, Genetics, Human Genome, DNA Methylation, DNA Mutational Analysis, Databases, Genetic, Genes, Neoplasm, Genetics, Medical, Genome, Human, Genomics, Humans, Intellectual Property, International Cooperation, Mutation, Neoplasms, International Cancer Genome Consortium, General Science & Technology
Abstract

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

Published
2010

3. International network of cancer genome projects.

Author

International Cancer Genome Consortium, Hudson, Thomas J, Anderson, Warwick, Artez, Axel, Barker, Anna D, Bell, Cindy, Bernabé, Rosa R, Bhan, MK, Calvo, Fabien, Eerola, Iiro, Gerhard, Daniela S, Guttmacher, Alan, Guyer, Mark, Hemsley, Fiona M, Jennings, Jennifer L, Kerr, David, Klatt, Peter, Kolar, Patrik, Kusada, Jun, Lane, David P, Laplace, Frank, Youyong, Lu, Nettekoven, Gerd, Ozenberger, Brad, Peterson, Jane, Rao, TS, Remacle, Jacques, Schafer, Alan J, Shibata, Tatsuhiro, Stratton, Michael R, Vockley, Joseph G, Watanabe, Koichi, Yang, Huanming, Yuen, Matthew MF, Knoppers, Bartha M, Bobrow, Martin, Cambon-Thomsen, Anne, Dressler, Lynn G, Dyke, Stephanie OM, Joly, Yann, Kato, Kazuto, Kennedy, Karen L, Nicolás, Pilar, Parker, Michael J, Rial-Sebbag, Emmanuelle, Romeo-Casabona, Carlos M, Shaw, Kenna M, Wallace, Susan, Wiesner, Georgia L, Zeps, Nikolajs, Lichter, Peter, Biankin, Andrew V, Chabannon, Christian, Chin, Lynda, Clément, Bruno, de Alava, Enrique, Degos, Françoise, Ferguson, Martin L, Geary, Peter, Hayes, D Neil, Johns, Amber L, Kasprzyk, Arek, Nakagawa, Hidewaki, Penny, Robert, Piris, Miguel A, Sarin, Rajiv, Scarpa, Aldo, van de Vijver, Marc, Futreal, P Andrew, Aburatani, Hiroyuki, Bayés, Mónica, Botwell, David DL, Campbell, Peter J, Estivill, Xavier, Grimmond, Sean M, Gut, Ivo, Hirst, Martin, López-Otín, Carlos, Majumder, Partha, Marra, Marco, McPherson, John D, Ning, Zemin, Puente, Xose S, Ruan, Yijun, Stunnenberg, Hendrik G, Swerdlow, Harold, Velculescu, Victor E, Wilson, Richard K, Xue, Hong H, Yang, Liu, Spellman, Paul T, Bader, Gary D, and Boutros, Paul C

Subjects
International Cancer Genome Consortium, Humans, Neoplasms, DNA Mutational Analysis, Genetics, Medical, Genomics, DNA Methylation, Mutation, Genome, Human, International Cooperation, Intellectual Property, Databases, Genetic, Genes, Neoplasm, Genetics, Medical, Genome, Human, Databases, Genetic, Genes, Neoplasm, General Science & Technology
Abstract

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

Published
2010

4. Complex landscapes of somatic rearrangement in human breast cancer genomes.

Author

Stephens, Philip J., McBride, David J., Meng-Lay Lin, Varela, Ignacio, Pleasance, Erin D., Simpson, Jared T., Stebbings, Lucy A., Leroy, Catherine, Edkins, Sarah, Mudie, Laura J., Greenman, Chris D., Mingming Jia, Latimer, Calli, Teague, Jon W., King Wai Lau, Burton, John, Quail, Michael A., Swerdlow, Harold, Churcher, Carol, and Natrajan, Rachael

Subjects
GENOMES, GENOMICS, GENES, CANCER genes, CANCER genetics, GENETICS, DNA repair, HEREDITY, DNA
Abstract

Multiple somatic rearrangements are often found in cancer genomes; however, the underlying processes of rearrangement and their contribution to cancer development are poorly characterized. Here we use a paired-end sequencing strategy to identify somatic rearrangements in breast cancer genomes. There are more rearrangements in some breast cancers than previously appreciated. Rearrangements are more frequent over gene footprints and most are intrachromosomal. Multiple rearrangement architectures are present, but tandem duplications are particularly common in some cancers, perhaps reflecting a specific defect in DNA maintenance. Short overlapping sequences at most rearrangement junctions indicate that these have been mediated by non-homologous end-joining DNA repair, although varying sequence patterns indicate that multiple processes of this type are operative. Several expressed in-frame fusion genes were identified but none was recurrent. The study provides a new perspective on cancer genomes, highlighting the diversity of somatic rearrangements and their potential contribution to cancer development. [ABSTRACT FROM AUTHOR]

Published
2009
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