COSMIC: High‐Resolution Cancer Genetics Using the Catalogue of Somatic Mutations in Cancer

S.A. Forbes1, D. Beare1, N. Bindal1, S. Bamford1, S. Ward1, C.G. Cole1, M. Jia1, C. Kok1, H. Boutselakis1, T. De1, Z. Sondka1, L. Ponting1, R. Stefancsik1, B. Harsha1, J. Tate1, E. Dawson1, S. Thompson1, H. Jubb1, P.J. Campbell1

1 Wellcome Trust Sanger Institute, Hinxton
Publication Name:  Current Protocols in Human Genetics
Unit Number:  Unit 10.11
DOI:  10.1002/cphg.21
Online Posting Date:  October, 2016
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

COSMIC (http://cancer.sanger.ac.uk) is an expert‐curated database of somatic mutations in human cancer. Broad and comprehensive in scope, recent releases in 2016 describe over 4 million coding mutations across all human cancer disease types. Mutations are annotated across the entire genome, but expert curation is focused on over 400 key cancer genes. Now encompassing the majority of molecular mutation mechanisms in oncogenetics, COSMIC additionally describes 10 million non‐coding mutations, 1 million copy‐number aberrations, 9 million gene‐expression variants, and almost 8 million differentially methylated CpGs. This information combines a consistent interpretation of the data from the major cancer genome consortia and cancer genome literature with exhaustive hand curation of over 22,000 gene‐specific literature publications. This unit describes the graphical Web site in detail; alternative protocols overview other ways the entire database can be accessed, analyzed, and downloaded. © 2016 by John Wiley & Sons, Inc.

Keywords: COSMIC; cancer; database; genetics; genomics; mutation; somatic

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Basic Protocol 1: Investigating the COSMIC Web Site
  • Alternate Protocol 1: The Cancer Browser
  • Alternate Protocol 2: The COSMIC Genome Browser
  • Alternate Protocol 3: Downloading Full Datasets
  • Alternate Protocol 4: Exploring the Oracle Database Directly
  • Commentary
  • Figures
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

Basic Protocol 1: Investigating the COSMIC Web Site

  Necessary ResourcesHardware
  • Any Internet‐connected computer or mobile device
Software
  • Web‐browsing software such as Internet Explorer, Firefox, Safari, Chrome
Files
  • No input files required

Alternate Protocol 1: The Cancer Browser

  Necessary ResourcesHardware
  • Any Internet‐connected computer (and an experienced bioinformatician)
Software
  • SFTP client software (e.g., WinSCP, CyberDuck, or UNIX command‐line)
  • Spreadsheet software or programming environment
Files
  • Input files are downloaded from the COSMIC SFTP site, described at http://cancer.sanger.ac.uk/cosmic/download

Alternate Protocol 2: The COSMIC Genome Browser

  Necessary ResourcesHardware
  • Any modern (post‐2010) computer should be sufficient to run a minimal Oracle install
Software
  • Oracle database (Oracle Standard Edition should suffice—COSMIC is currently tested for Oracle version 11.2 only)
Files
  • Input files are downloaded from the COSMIC SFTP site, here: http://cancer.sanger.ac.uk/cosmic/download (for instance, Feb 2016, v76 is available at http://cancer.sanger.ac.uk/cosmic/files?data=/files/grch38/cosmic/v76/COSMIC_ORACLE_EXPORT.dmp.gz)
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
  1000 Genomes Project Consortium. 2015. A global reference for human genetic variation. Nature 526:68‐74. doi: 10.1038/nature15393.
  Bamford, S., Dawson, E., Forbes, S., Clements, J., Pettett, R., Dogan, A., Flanagan, A., Teague, J., Futreal, P.A., Stratton, M.R., and Wooster, R. 2004. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br. J. Cancer. 91:355‐358. doi: 10.1038/sj.bjc.6601894
  Futreal, P.A., Coin, L., Marshall, M., Down, T., Hubbard, T., Wooster, R., Rahman, N., and Stratton, M.R. 2004. A census of human cancer genes. Nat. Rev. Cancer 4:177‐183. doi: 10.1038/nrc1299
  Gossage, L., Eisen, T., and Maher, E.R. 2015. VHL, the story of a tumour suppressor gene. Nat. Rev. Cancer 15:55‐64. doi:10.1038/nrc3844
  Long, G.V., Fung, C., Menzies, A.M., Pupo, G.M., Carlino, M.S., Hyman, J., Shahheydari, H,. Tembe, V., Thompson, J.F., Saw, R.P., Howle, J., Hayward, N.K., Johansson, P., Scolyer, R.A., Kefford, R.F., and Rizos, H. 2014. Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy ofBRAF‐mutant metastatic melanoma. Nat. Commun. 5:5694. doi: 10.1038/ncomms6694.
  Malone, J., Holloway, E., Adamusiak, T., Kapushesky, M., Zheng, J., Kolesnikov, N., Zhukova, A., Brazma, A., and Parkinson, H. 2010. Modeling sample variables with an Experimental Factor Ontology. Bioinformatics 26:1112‐1118. doi: 10.1093/bioinformatics/btq099
  McLendon, R., Friedman, A., Bigner, D., Van Meir, E.G., Brat, D.J., Mastrogianakis, M.G., Olson, J.J., Mikkelsen, T., Lehman, N., Aldape, K., Yung, W.K., Bogler, O., Weinstein, J.N., VandenBerg, S., Berger, M., Prados, M., Muzny, D., Morgan, M., Scherer, S., Sabo, A., Nazareth, L., Lewis, L., Hall, O., Zhu, Y., Ren, Y., Alvi, O., Yao, J., Hawes, A., Jhangiani, S., Fowler, G., San Lucas, A., Kovar, C., Cree, A., Dinh, H., Santibanez, J., Joshi, V., Gonzalez‐Garay, M.L., Miller, C.A., Milosavljevic, A., Donehower, L., Wheeler, D.A., Gibbs, R.A., Cibulskis, K., Sougnez, C., Fennell, T., Mahan, S., Wilkinson, J., Ziaugra, L., Onofrio, R., Bloom, T., Nicol, R., Ardlie, K., Baldwin, J., Gabriel, S., Lander, E.S., Ding, L., Fulton, R.S., McLellan, M.D., Wallis, J., Larson, D.E., Shi, X., Abbott, R., Fulton, L., Chen, K., Koboldt, D.C., Wendl, M.C., Meyer, R., Tang, Y., Lin, L., Osborne, J.R., Dunford‐Shore, B.H., Miner, T.L., Delehaunty, K., Markovic, C., Swift, G., Courtney, W., Pohl, C., Abbott, S., Hawkins, A., Leong, S., Haipek, C., Schmidt, H., Wiechert, M., Vickery, T., Scott, S., Dooling, D.J., Chinwalla, A., Weinstock, G.M., Mardis, E.R., Wilson, R.K., Getz, G., Winckler, W., Verhaak, R.G., Lawrence, M.S., O'Kelly M., Robinson, J., Alexe, G., Beroukhim, R., Carter, S., Chiang, D., Gould, J., Gupta, S., Korn, J., Mermel, C., Mesirov, J., Monti S, Nguyen, H., Parkin, M., Reich, M., Stransky, N., Weir, B.A., Garraway, L., Golub, T., Meyerson, M., Chin, L., Protopopov, A., Zhang, J., Perna, I., Aronson, S., Sathiamoorthy, N., Ren, G., Yao, J., Wiedemeyer, W.R., Kim, H., Kong, S.W., Xiao, Y., Kohane, I.S., Seidman, J., Park, P.J., Kucherlapati, R., Laird, P.W., Cope, L., Herman, J.G., Weisenberger, D.J., Pan, F., Van den Berg, D., Van Neste, L., Yi, J.M., Schuebel, K.E., Baylin, S.B., Absher, D.M., Li, J.Z., Southwick, A., Brady, S., Aggarwal, A., Chung, T., Sherlock, G., Brooks, J.D., Myers, R.M., Spellman, P.T., Purdom, E., Jakkula, L.R., Lapuk, A.V., Marr, H., Dorton, S., Choi, YG., Han, J., Ray, A., Wang, V., Durinck, S., Robinson, M., Wang, NJ., Vranizan, K., Peng, V., Van Name, E., Fontenay, G.V., Ngai, J., Conboy, J.G., Parvin, B., Feiler, H.S., Speed, T.P., Gray, J.W., Brennan, C., Socci, N.D., Olshen, A., Taylor, B.S., Lash, A., Schultz, N., Reva, B., Antipin, Y., Stukalov, A., Gross, B., Cerami, E., Wang, W.Q., Qin, L.X., Seshan, V.E., Villafania, L., Cavatore, M., Borsu, L., Viale, A., Gerald, W., Sander, C., Ladanyi, M., Perou, CM., Hayes, D.N., Topal, M.D., Hoadley, K.A., Qi, Y., Balu, S., Shi, Y., Wu, J., Penny, R., Bittner, M., Shelton, T., Lenkiewicz, E., Morris, S., Beasley, D., Sanders, S., Kahn, A., Sfeir, R., Chen, J., Nassau, D., Feng, L., Hickey, E., Barker, A., Gerhard, D.S., Vockley, J., Compton, C., Vaught, J., Fielding, P., Ferguson, M.L., Schaefer, C., Zhang, J., Madhavan, S., Buetow, K.H., Collins, F., Good, P., Guyer, M., Ozenberger, B., Peterson, J., and Thomson, E. (2008‐10‐23). Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061‐1068. doi: 10.1038/nature07385.
  Oren, M. and Rotter, V. 2010. Mutant p53 gain‐of‐function in cancer. Cold Spring Harb Perspect Biol. 2:a001107. doi: 10.1101/cshperspect.a001107.
  Pfeifer, G.P., Denissenko, M.F., Olivier, M., Tretyakova, N., Hecht, S.S., and Hainaut, P. 2002. Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking‐associated cancers. Oncogene 21:7435‐7451. doi:10.1038/sj.onc.1205803
  Pruitt, K.D., Harrow, J., Harte, R.A., Wallin, C., Diekhans, M., Maglott, D.R., Searle, S., Farrell, C.M., Loveland, J.E., Ruef, B.J., Hart, E., Suner, M.M., Landrum, M.J., Aken, B., Ayling, S., Baertsch, R., Fernandez‐Banet, J., Cherry, J.L., Curwen, V., Dicuccio, M., Kellis, M., Lee, J., Lin, M.F., Schuster, M., Shkeda, A., Amid, C., Brown, G., Dukhanina, O., Frankish, A., Hart, J., Maidak, B.L., Mudge, J., Murphy, M.R., Murphy, T., Rajan, J., Rajput, B., Riddick, L.D., Snow, C., Steward, C., Webb, D., Weber, J.A., Wilming, L., Wu, W., Birney, E., Haussler, D., Hubbard, T., Ostell, J., Durbin, R., and Lipman, D. 2009. The consensus coding sequence (CCDS) project: Identifying a common protein‐coding gene set for the human and mouse genomes. Genome Res. 19:1316‐1323. doi: 10.1101/gr.080531.108.
  Reddy, E.P., Reynolds, R.K., Santos, E., and Barbacid, M. 1982. A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature 300:149‐152. doi: 10.1101/gr.080531.108.
  Richardson, C.J., Gao, Q., Mitsopoulous, C., Zvelebil, M., Pearl, L.H., and Pearl, F.M. 2009. MoKCa database‐mutations of kinases in cancer. Nucleic Acids Res. 37:D824‐D831. doi: 10.1093/nar/gkn832.
  Sánchez‐Vega, F., Gotea, V., Petrykowska, H.M., Margolin, G., Krivak, T.C., DeLoia, J.A., Bell, D.W., and Elnitski, L. 2013. Recurrent patterns of DNA methylation in the ZNF154, CASP8, and VHL promoters across a wide spectrum of human solid epithelial tumors and cancer cell lines. Epigenetics 8:1355‐1372. doi: 10.4161/epi.26701.
  Scheffzek, K., Ahmadian, M.R., Kabsch, W., Wiesmuller, L., Lautwein, A., Schmitz, F., and Wittinghofer, A. 1997. The Ras‐RasGAP complex: Structural basis for GTPase activation and its loss in oncogenic RAS mutants. Science 277:333‐338. doi: 10.1126/science.277.5324.333.
  Shepherd, R., Forbes, S.A., Beare, D., Bamford, S., Cole, C.G., Ward, S., Bindal, N., Gunasekaran, P., Jia, M., Kok, C.Y., Leung, K., Menzies, A., Butler, A.P., Teague, J.W., Campbell, P.J., Stratton, M.R., and Futreal, P.A. 2011. Data mining using the catalogue of somatic mutations in cancer BioMart. Database 2011:bar018. doi: 10.1093/database/bar018.
  Song, H., Hollstein, M., and Xu, Y. 2007. p53 gain‐of‐function cancer mutants induce genetic instability by inactivating ATM. Nat. Cell Biol. 9:573‐580. doi: 10.1038/ncb1571.
  Yates, A., Akanni, W., Amode, M.R., Barrell, D., Billis, K., Carvalho‐Silva, D., Cummins, C., Clapham, P., Fitzgerald, S., Gil, L., Girón, C.G., Gordon, L., Hourlier, T., Hunt, S.E., Janacek, S.H., Johnson, N., Juettemann, T., Keenan, S., Lavidas, I., Martin, F.J., Maurel, T., McLaren, W., Murphy, D.N., Nag, R., Nuhn, M., Parker, A., Patricio, M., Pignatelli, M., Rahtz, M., Riat, H.S., Sheppard, D., Taylor, K., Thormann, A., Vullo, A., Wilder, S.P., Zadissa, A., Birney, E., Harrow, J., Muffato, M., Perry, E., Ruffier, M., Spudich, G., Trevanion, S.J., Cunningham, F., Aken, B.L., Zerbino, D.R., and Flicek, P. 2016. Ensembl 2016. Nucleic Acids Res. 44:D710‐716.
  Zerbino, D.R., Wilder, S.P., Johnson, N., Juettemann, T., and Flicek, P.R. 2015. The ensembl regulatory build. Genome Biol. 16:56. doi: 10.1186/s13059‐015‐0621‐5
  Zhang, J., Baran, J., Cros, A., Guberman, J.M., Haider, S., Hsu, J., Liang, Y., Rivkin, E., Wang, J., Whitty, B., Wong‐Erasmus, M., Yao, L., and Kasprzyk, A. 2011. International Cancer Genome Consortium Data Portal—A one‐stop shop for cancer genomics data. Database 2011:bar026. doi: 10.1093/database/bar026.
  Zhou, X., Edmonson, M.N., Wilkinson, M.R., Patel, A., Wu, G., Liu, Y., Li, Y., Zhang, Z., Rusch, M.C., Parker, M., Becksfort, J., Downing, J.R., and Zhang, J. 2016. Exploring genomic alteration in pediatric cancer using ProteinPaint. Nat. Genet. 48:4‐6. doi: 10.1038/ng.3466.
Internet Resources
  http://www.sanger.ac.uk/cosmic
  COSMIC home page.
  http://cancer.sanger.ac.uk/genome
  COSMIC genome browser.
  http://www.sanger.ac.uk/genetics/cgp/census
  Cancer Gene Census.
  http://cancer.sanger.ac.uk/cell_lines
  COSMIC cell lines.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library