The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags

doi:10.1073/pnas.1233632100

The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags

Helena Brentania,
Otávia L. Caballeroa,
Anamaria A. Camargoa,
Aline M. da Silvab,
Wilson Araújo da Silva, Jr.c,
Emmanuel Dias Netod,
Marco Grivete,
Arthur Gruberf,
Pedro Edson Moreira Guimaraesd,
Winston Hideg,
Christian Iselih,
C. Victor Jongeneelh,
Janet Kelsog,
Maria Aparecida Nagaii,
Elida Paula Benquique Ojopid,
Elisson C. Osorioa,
Eduardo M. R. Reisb,
Gregory J. Rigginsj,
Andrew John George Simpsona,k,
Sandro de Souzaa,
Brian J. Stevensonh,
Robert L. Strausbergl,
Eloiza H. Tajaram,
Sergio Verjovski-Almeidab,
The Human Cancer Genome Project Cancer Genome Anatomy Project Annotation Consortium*, and
The Human Cancer Genome Project Sequencing Consortium†

ⁱLaboratorio de Genética Molecular do Cancer, Departmento de Radiologia, Universidade de São Paulo, Travessa da Rua Dr. Ovídeo Pires de Campos S/N, 4° andar, 05403-010, São Paulo, SP, Brazil; ^bDepartamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-900, São Paulo, SP, Brazil; ^mDepartamento de Biologia, Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, 15054, São José do Rio Preto, SP, Brazil; ^aLudwig Institute for Cancer Research, Rua Professor Antonio Prudente 109 4° andar, 01509-010, São Paulo, SP, Brazil; ^fDepartamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, Avenida Professor Orlando Marques de Paiva 87, 05508-000, São Paulo, SP, Brazil; ^cFundação Hemocentro de Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Rua Tenente Catão Roxo 2501, 14051-140, Ribeirão Preto, SP, Brazil; ^dLaboratory of Neurosciences (LIM-27), Instituto de Psiquiatria, Faculdade de Medicina, Universidade de São Paulo, Rua Dr. Ovidio de Campos, S/N, 05403-010, São Paulo, SP, Brazil; ^lNational Cancer Institute, Bethesda, MD 20892; ^jDuke University Medical Center, Durham, NC 27710; ^gSouth African National Bioinformatics Institute, University of the Western Cape, Private Bag X17, 7535 Bellville, South Africa; ^hOffice of Information Technology, Ludwig Institute for Cancer Research, CH-1066 Épalinges, Switzerland; and ^eCentro de Estudo de Telecomunicações-PUC, Rua Marquês de São Vicente, 225, 22453-900, Rio de Janeiro, RJ, Brazil

Contributed by Walter Bodmer, June 12, 2003

Abstract

Whereas genome sequencing defines the genetic potential of an organism, transcript sequencing defines the utilization of this potential and links the genome with most areas of biology. To exploit the information within the human genome in the fight against cancer, we have deposited some two million expressed sequence tags (ESTs) from human tumors and their corresponding normal tissues in the public databases. The data currently define ≈23,500 genes, of which only ≈1,250 are still represented only by ESTs. Examination of the EST coverage of known cancer-related (CR) genes reveals that <1% do not have corresponding ESTs, indicating that the representation of genes associated with commonly studied tumors is high. The careful recording of the origin of all ESTs we have produced has enabled detailed definition of where the genes they represent are expressed in the human body. More than 100,000 ESTs are available for seven tissues, indicating a surprising variability of gene usage that has led to the discovery of a significant number of genes with restricted expression, and that may thus be therapeutically useful. The ESTs also reveal novel nonsynonymous germline variants (although the one-pass nature of the data necessitates careful validation) and many alternatively spliced transcripts. Although widely exploited by the scientific community, vindicating our totally open source policy, the EST data generated still provide extensive information that remains to be systematically explored, and that may further facilitate progress toward both the understanding and treatment of human cancers.

Footnotes

↵ k To whom correspondence should be addressed. E-mail: asimpson{at}licr.org.
↵ * The Human Cancer Genome Project/Cancer Genome Anatomy Project Annotation Consortium: Marcio Luis Acencioⁿ, Mário Henrique Bengtson^o, Fabiana Bettoni^p, Walter F. Bodmer^q, Marcelo R. S. Briones^r, Luiz Paulo Camargo^s, Webster Cavenee^t, Janete M. Cerutti^u, Luís Eduardo Coelho Andrade^v, Paulo César Costa dos Santosⁿ, Maria Cristina Ramos Costa^w, Israel Tojal da Silva^w, Marcos Roberto H. Estécio^x, Karine Sa Ferreira^w, Frank B. Furnari^t, Milton Faria, Jr.^s, Pedro A. F. Galante^p, Gustavo S. Guimaraes^y, Adriano Jesus Holanda^w, Edna Teruko Kimura^z, Maarten R Leerkes^p, Xin Lu^aa, Rui M. B. Maciel^u, Elizabeth A. L. Martins^bb, Katlin Brauer Massirer^o, Analy S. A. Melo^r, Carlos Alberto Mestriner^cc, Elisabete Cristina Miraccaⁿ, Leandro Lorenco Miranda^s, Francisco G. Nobrega^dd, Paulo S. Oliveira^p, Apuã C. M. Paquola^ee, José Rodrigo C. Pandolfi^cc, Maria Inês de Moura Campos Pardini^ff, Fabio Passetti^p, John Quackenbush^gg, Beatriz Schnabel^r, Mari Cleide Sogayar^o, Jorge E. Souza^p, Sandro R. Valentini^cc, and Andre C. Zaiats^p.
↵ † The Human Cancer Genome Project Sequencing Consortium: Elisabete Jorge Amaral^x, Liliane A. T. Arnaldi^u, Amélia Goes de Araújo^w, Simone Aparecida de Bessaⁿ, David C. Bicknell^q, Maria Eugenia Ribeiro de Camaro^y, Dirce Maria Carraro^p, Helaine Carrer^hh, Alex F. Carvalho^p, Christian Colin^o, Fernando Costaⁱⁱ, Cyntia Curcio^z, Ismael Dale Cotrim Guerreiro da Silva^w, Neusa Pereira da Silva^v,Márcia Dellamano^p, Hamza El-Dorry^kk, Enilza Maria Espreafico^ll, Ari José Scattone Ferreira^kk, Cristiane Ayres Ferreira^w, Maria Angela H. Z. Fortes^mm, Angelita Habr Gamaⁿⁿ, Daniel Giannella-Neto^mm, Maria Lúcia C. C. Giannella^mm, Ricardo R. Giorgi^mm, Gustavo Henrique Goldman^oo, Maria Helena S. Goldman^pp, Christine Hackel^y, Paulo Lee Ho^bb, Elza Myiuki Kimura^qq, Luiz Paulo Kowalski^rr, Jose E. Krieger^ss, Luciana C. C. Leite^bb, Ademar Lopes^rr, Ana Mercedes S. C. Luna^mm, Alan Mackay^tt, Suely Kazue Nagahashi Mariⁿ, Adriana Aparecida Marques^w, Waleska K. Martins^p, André Montagnini^rr, Mario Mourão Neto^rr, Ana Lucia T. O. Nascimento^bb, A. Munro Neville^uu, Marina P. Nobrega^dd, Mike J. O'Hare^tt, Audrey Yumi Otsuka^vv, Anna Izabel Ruas de Melo^p, Maria Luisa Paçó-Larson^ww, Gonçalo Guimarães Pereiraⁱⁱ, Neusa Pereira da Silva^v, João Bosco Pesquero^jj, Juliana Gilbert Pessoa^jj, Paula Rahal^x, Claudia Aparecida Rainho^xx, Vanderlei Rodrigues^yy, Silvia Regina Rogatto^xx, Camila Malta Romano^zz, Janaína Gusmão Romeiro^x, Benedito Mauro Rossi^rr, Monica Rusticciⁿ, Renata Guerra de Sá^yy, Simone Cristina Sant' Anna^qq, Míriam L. Sarmazo^x, Teresa Cristina de Lima e Silva^y, Fernando Augusto Soares^rr, Maria de Fátima Sonati^qq, Josane de Freitas Sousa^ll, Diana Queiroz^y, Valéria Valente^ww, André Luiz Vettore^p, Fabiola Elizabeth Villanova^vv, Marco Antonio Zago^w, and Heloisa Zalcberg^p.

↵ † ⁿLaboratorio de Genética Molecular do Cancer, and ⁿⁿDepartment of Gastroenterology, Faculdade de Medicina, Universidade de São Paulo, Travessa da Rua Dr. Ovídeo Pires de Campos S/N, 4° andar, 05403-010, São Paulo, SP, Brazil; ^eeDepartamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-900, São Paulo, SP, Brazil; ^bbInstituto Butantan, Avenida Vital Brazil 1500, 05503-900, São Paulo, Brazil; ^wwDepartamento de Biologia Celular e Molecular e de Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049-900, Ribeirão Preto, SP, Brazil; ^uLaboratory of Molecular Endocrinology, Department of Medicine, Federal University of São Paulo, Rua Pedro de Toledo 781, 12th Floor, 04023-039, São Paulo, SP, Brazil; ^oChemistry Institute, University of São Paulo, 05513-970, São Paulo, SP, Brazil; ^yyDepartamento de Bioquimica e Imunologia, and ^llDepartamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049-900, Ribeirão Preto, SP, Brazil; ^jjDepartment of Biophysics, and ^rDepartamento de Microbiologia, Imunologia, e Parasitologia, Universidade Federal de São Paulo, Rua Botucatu, 862 3° andar, 04023-062, São Paulo, SP, Brazil; ^ffLaboratório de Biologia Molecular, Hemocentro, Faculdade de Medicina Universidade Estidual Paulista, 18618-000, Botucatu, SP, Brazil; ^sDepartamento de Bioinformática-UNAERP, Universidade de Ribeirao Preto, 14096-380, Ribeirão Preto, SP, Brazil; ^zDepartamento de Histologia e Embriologia, Instituto de Ciencias Biomedicas, Universidade de São Paulo, Avenida Prof Lineu Prestes 1524, 05508-900, São Paulo, Brazil; ^ssDepartment of Medicine, Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), Universidade de São Paulo, 05403-000, São Paulo, SP, Brazil; ^xDepartamento de Biologia, Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, 15054, São José do Rio Preto, SP, Brazil; ^qqDepartment of Clinical Pathology, School of Medical Sciences, State University of Campinas-UNICAMP, 13083-970 Campinas, SP, Brazil; ^pLudwig Institute for Cancer Research, Rua Professor Antonio Prudente 109, 4° andar, 01509-010, São Paulo, SP, Brazil; ^rrFundação Antonio Prudente, Hospital do Câncer, Rua Professor Antonio Prudente 211, 01509-900, São Paulo, SP, Brazil; ^zzDepartamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, Avenida Professor Orlando Marques de Paiva 87, 05508-000, São Paulo, SP, Brazil; ^wFundação Hemocentro de Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Rua Tenente Catão Roxo 2501, 14051-140, Ribeirão Preto, SP, Brazil; ^ddInstituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, 12244-000, São José dos Campos, SP, Brazil; ^hhDepartment of Biological Sciences, Escola Superior de Agricultura “Luiz de Queiroz,” Universidade de São Paulo, 13418-900, Piracicaba, SP, Brazil; ^vDepartamento de Reumatologia, Universidade Federal de São Paulo, Rua Botucatu 740, 04023-062, São Paulo, SP, Brazil; ^kkDepartment of Biochemistry, Institute of Chemistry, University of Sao Paulo, Avenida Professor Lineu Prestes 748, 05508-900, São Paulo, SP, Brazil; ^ccDepartamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Estadual Paulista, 14801-902, São Paulo, Brazil; ^xxDepartamento de Genética, Instituto de Biociências, Universidade Estadual Paulista, 18618-970, Botucatu, SP, Brazil; ^vvGynecology Department, Federal University of Sao Paulo, Rua Botucatu 740, 04023-062, São Paulo, SP, Brazil; ^ooFaculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de São Paulo, Avenida do Cafe S/N, 14040-903, Ribeirao Preto, SP, Brazil; ^ppFaculdade de Filosofia, Ciências e Letras, Universidade de São Paulo, Avenida Bandeirantes, 3900, 14040-901, Ribeirão Preto, SP, Brazil; ^mmLaboratory for Cellular and Molecular Endocrinology (LIM-25/HCFMUSP), School of Medicine, Universidade de São Paulo, Avenida Dr. Arnaldo, 455 no. 4305, 01246-903, São Paulo, SP, Brazil; ^yDepartamento de Genética e Evolução, State University of Campinas-UNICAMP, 13083-970, Campinas, SP, Brazil; ⁱⁱNational Cancer Institute, Bethesda, MD 20892; ^qCancer Research U.K. Cancer and Immunogenetics Laboratory, Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom; ^tLudwig Institute for Cancer Research, Department of Medicine, Center for Molecular Genetics, University of California at San Diego, La Jolla, CA 92093-0660; ^aaLudwig Institute for Cancer Research, Imperial College School of Medicine, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom; ^ggThe Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850; ^ttLudwig Institute for Cancer Research, Breast Cancer Laboratory, Department of Surgery, Royal Free and University College Medical School, 67-73 Riding House Street, London W1W 7EJ, United Kingdom; and ^uuLudwig Institute for Cancer Research, Horatio House, 77-85 Fulham Palace Road, London W6 8JC, United Kingdom.
Abbreviations: EST, expressed sequence tag; CGAP, Cancer Genome Anatomy Project; HCGP, Human Cancer Genome Project; SNP, single-nucleotide polymorphism; CR, cancer-related.
↵ ‡ The Human Cancer Genome Project/Cancer Genome Anatomy Project Annotation Consortium, Jamborestes, Aug. 20-25, 2001, São Paulo, Brazil.