1. Large-scale Transcriptome Analyses Reveal New Genetic Marker Candidates of Head, Neck, and Thyroid Cancer
- Author
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Reis, Eduardo M., Ojopi, Elida PB, Alberto, Fernando L., Rahal, Paula, Tsukumo, Fernando, Mancini, Ulises M., Guimaraes, Gustavo Stuani [UNIFESP], Thompson, Gloria MA, Camacho, Cleber [UNIFESP], Miracca, Elisabete, Carvalho, Andre L., Machado, Abimael A., Paquola, Apuã CM, Cerutti, Janete M. [UNIFESP], Silva, Aline M. da, Pereira, Gonçalo G., Valentini, Sandro R, Nagai, Maria A., Kowalski, Luiz Paulo, Verjovski-Almeida, Sergio, Tajara, Eloiza H., Dias-Neto, Emmanuel, Bengtson, Mario H., Canevari, Renata A., Carazzolle, Marcelo F., Colin, Christian, Costa, Fernando F., Costa, Maria Cristina, Estecio, Marcos R., Esteves, Leda Isabel, Federico, Miriam H., Guimaraes, Pedro Edson, Hackel, Christine, Kimura, Edna T., Leoni, Suzana G., Maciel, Ru M., Maistro, Simone, Mangone, Flavia R., Massirer, Katlin B., Matsuo, Silvia E., Nobrega, Francisco G., Nobrega, Marina Pasetto, Nunes, Diana Noronha, Nunes, Fabio, Pandolfi, Jose Rodrigo, Pardini, Maria Inês, Pasini, Fatima Solange, Peres, Tarcisio, Rainho, Claudia Aparecida, Reis, Patricia P. dos, Rodrigus-Lisoni, Flavia Cristina, Rogatto, Silvia Regina, Santos, Andrey dos, Santos, Paulo C. dos, Sogayar, Mari Cleide, Zanelli, Cleslei F., Head and Neck Annotation Consortiu, Universidade de São Paulo (USP), Universidade Federal de São Paulo (UNIFESP), Hosp Canc AC Camargo, Universidade Estadual de Campinas (UNICAMP), Univ Estadual Paulista, and Fac Med Sao Jose Rio Preto
- Subjects
Genetic Markers ,Cancer Research ,Transcription, Genetic ,Thyroid Gland ,Biology ,Polymerase Chain Reaction ,DNA sequencing ,Intergenic region ,Gene mapping ,Humans ,Protein Isoforms ,RNA, Messenger ,Thyroid Neoplasms ,Gene ,Expressed Sequence Tags ,Genetics ,Mouth ,Expressed sequence tag ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Alternative splicing ,Sequence Analysis, DNA ,Gene expression profiling ,Alternative Splicing ,Oncology ,Head and Neck Neoplasms ,Pharynx ,Human genome ,Larynx - Abstract
A detailed genome mapping analysis of 213,636 expressed sequence tags (EST) derived from nontumor and tumor tissues of the oral cavity, larynx, pharynx, and thyroid was done. Transcripts matching known human genes were identified; potential new splice variants were flagged and subjected to manual curation, pointing to 788 putatively new alternative splicing isoforms, the majority (75%) being insertion events. A subset of 34 new splicing isoforms (5% of 788 events) was selected and 23 (68%) were confirmed by reverse transcription-PCR and DNA sequencing. Putative new genes were revealed, including six transcripts mapped to well-studied chromosomes such as 22, as well as transcripts that mapped to 253 intergenic regions. in addition, 2,251 noncoding intronic RNAs, eventually involved in transcriptional regulation, were found. A set of 250 candidate markers for loss of heterozygosis or gene amplification was selected by identifying transcripts that mapped to genomic regions previously known to be frequently amplified or deleted in head, neck, and thyroid tumors. Three of these markers were evaluated by quantitative reverse transcription-PCR in an independent set of individual samples. Along with detailed clinical data about tumor origin, the information reported here is now publicly available on a dedicated Web site as a resource for further biological investigation. This first in silico reconstruction of the head, neck, and thyroid transcriptomes points to a wealth of new candidate markers that can be used for future studies on the molecular basis of these tumors. Similar analysis is warranted for a number of other tumors for which large EST data sets are available. Univ São Paulo, Fac Med, Inst Psiquiatria, Neurosci Lab,Dept Psiquiatria, BR-05403010 São Paulo, Brazil Univ São Paulo, Fac Med, Dept Bioquim, BR-05403010 São Paulo, Brazil Univ São Paulo, Fac Med, Lab Bioinformat, Inst Quim, BR-05403010 São Paulo, Brazil Univ São Paulo, Fac Med, Disciplina Oncol, Dept Radiol, BR-05403010 São Paulo, Brazil Universidade Federal de São Paulo, Mol Endocrinol Lab, Dept Med & Morfol, São Paulo, Brazil Hosp Canc AC Camargo, Dept Cirurg Cabeca & Pescoco & Otorrinolaringolog, São Paulo, SP, Brazil Univ Estadual Campinas, Inst Biol, Dept Genet & Evolucao, Lab Biol Mol & Genom Hemoctr, Campinas, SP, Brazil Univ Estadual Campinas, Inst Biol, Dept Genet & Evolucao, Lab Genom & Expressao, Campinas, SP, Brazil Univ Estadual Paulista, Dept Biol, Inst Biociencias, Araraquara, SP, Brazil Fac Med Sao Jose Rio Preto, Dept Biol Mol, Sao Jose de Rio Preto, SP, Brazil Univ Estadual Paulista, Escola Farm, Dept Ciencias Biol, Araraquara, SP, Brazil Universidade Federal de São Paulo, Mol Endocrinol Lab, Dept Med & Morfol, São Paulo, Brazil Web of Science
- Published
- 2005