title: Large-scale transcriptome analyses reveal new genetic marker candidates of head, neck, and thyroid cancer.
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.
authors.affiliation: Departamento de Bioquímica, Faculdade de Medicina, Universidade de São Paulo, Brazil.
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Reis
authors.forename: Elida P B
authors.initials: EP
authors.lastname: Ojopi
authors.forename: Fernando L
authors.initials: FL
authors.lastname: Alberto
authors.forename: Paula
authors.initials: P
authors.lastname: Rahal
authors.forename: Fernando
authors.initials: F
authors.lastname: Tsukumo
authors.forename: Ulises M
authors.initials: UM
authors.lastname: Mancini
authors.forename: Gustavo S
authors.initials: GS
authors.lastname: Guimarães
authors.forename: Gloria M A
authors.initials: GM
authors.lastname: Thompson
authors.forename: Cleber
authors.initials: C
authors.lastname: Camacho
authors.forename: Elisabete
authors.initials: E
authors.lastname: Miracca
authors.forename: André L
authors.initials: AL
authors.lastname: Carvalho
authors.forename: Abimael A
authors.initials: AA
authors.lastname: Machado
authors.forename: Apuã C M
authors.initials: AC
authors.lastname: Paquola
authors.forename: Janete M
authors.initials: JM
authors.lastname: Cerutti
authors.forename: Aline M
authors.initials: AM
authors.lastname: da Silva
authors.forename: Gonçalo G
authors.initials: GG
authors.lastname: Pereira
authors.forename: Sandro R
authors.initials: SR
authors.lastname: Valentini
authors.forename: Maria A
authors.initials: MA
authors.lastname: Nagai
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Kowalski
authors.forename: Sergio
authors.initials: S
authors.lastname: Verjovski-Almeida
authors.forename: Eloiza H
authors.initials: EH
authors.lastname: Tajara
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dias-Neto
authors.forename: Mario H
authors.initials: MH
authors.lastname: Bengtson
authors.forename: Renata A
authors.initials: RA
authors.lastname: Canevari
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Carazzolle
authors.forename: Christian
authors.initials: C
authors.lastname: Colin
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Costa
authors.forename: Maria Cristina R
authors.initials: MC
authors.lastname: Costa
authors.forename: Marcos R H
authors.initials: MR
authors.lastname: Estécio
authors.forename: Leda Isabel C V
authors.initials: LI
authors.lastname: Esteves
authors.forename: Miriam H H
authors.initials: MH
authors.lastname: Federico
authors.forename: Pedro Edson Moreira
authors.initials: PE
authors.lastname: Guimarães
authors.forename: Christine
authors.initials: C
authors.lastname: Hackel
authors.forename: Edna T
authors.initials: ET
authors.lastname: Kimura
authors.forename: Suzana G
authors.initials: SG
authors.lastname: Leoni
authors.forename: Ru M B
authors.initials: RM
authors.lastname: Maciel
authors.forename: Simone
authors.initials: S
authors.lastname: Maistro
authors.forename: Flavia R R
authors.initials: FR
authors.lastname: Mangone
authors.forename: Katlin B
authors.initials: KB
authors.lastname: Massirer
authors.forename: Silvia E
authors.initials: SE
authors.lastname: Matsuo
authors.forename: Francisco G
authors.initials: FG
authors.lastname: Nobrega
authors.forename: Marina Pasetto
authors.initials: MP
authors.lastname: Nóbrega
authors.forename: Diana Noronha
authors.initials: DN
authors.lastname: Nunes
authors.forename: Fabio
authors.initials: F
authors.lastname: Nunes
authors.forename: José Rodrigo
authors.initials: JR
authors.lastname: Pandolfi
authors.forename: Maria Inês M C
authors.initials: MI
authors.lastname: Pardini
authors.forename: Fátima Solange
authors.initials: FS
authors.lastname: Pasini
authors.forename: Tarcisio
authors.initials: T
authors.lastname: Peres
authors.forename: Cláudia Aparecida
authors.initials: CA
authors.lastname: Rainho
authors.forename: Patrícia P
authors.initials: PP
authors.lastname: dos Reis
authors.forename: Flávia Cristina C
authors.initials: FC
authors.lastname: Rodrigus-Lisoni
authors.forename: Silvia Regina
authors.initials: SR
authors.lastname: Rogatto
authors.forename: Andrey
authors.initials: A
authors.lastname: dos Santos
authors.forename: Paulo C C
authors.initials: PC
authors.lastname: dos Santos
authors.forename: Mar Cleide
authors.initials: MC
authors.lastname: Sogayar
authors.forename: Cleslei F
authors.initials: CF
authors.lastname: Zanelli
mesh_terms: D017398:Alternative Splicing; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007830:Larynx / Q000378:metabolism; D009055:Mouth / Q000378:metabolism; D010614:Pharynx / Q000378:metabolism; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D005819:Genetic Markers; D020033:Protein Isoforms; D012333:RNA, Messenger