Large-scale transcriptome analyses reveal new genetic marker candidates of head, neck, and thyroid cancer.
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.
Reis
Eduardo M
EM
Departamento de Bioquímica, Faculdade de Medicina, Universidade de São Paulo, Brazil.
Ojopi
Elida P B
EP
Alberto
Fernando L
FL
Rahal
Paula
P
Tsukumo
Fernando
F
Mancini
Ulises M
UM
Guimarães
Gustavo S
GS
Thompson
Gloria M A
GM
Camacho
Cleber
C
Miracca
Elisabete
E
Carvalho
André L
AL
Machado
Abimael A
AA
Paquola
Apuã C M
AC
Cerutti
Janete M
JM
da Silva
Aline M
AM
Pereira
Gonçalo G
GG
Valentini
Sandro R
SR
Nagai
Maria A
MA
Kowalski
Luiz Paulo
LP
Verjovski-Almeida
Sergio
S
Tajara
Eloiza H
EH
Dias-Neto
Emmanuel
E
Bengtson
Mario H
MH
Canevari
Renata A
RA
Carazzolle
Marcelo F
MF
Colin
Christian
C
Costa
Fernando F
FF
Costa
Maria Cristina R
MC
Estécio
Marcos R H
MR
Esteves
Leda Isabel C V
LI
Federico
Miriam H H
MH
Guimarães
Pedro Edson Moreira
PE
Hackel
Christine
C
Kimura
Edna T
ET
Leoni
Suzana G
SG
Maciel
Ru M B
RM
Maistro
Simone
S
Mangone
Flavia R R
FR
Massirer
Katlin B
KB
Matsuo
Silvia E
SE
Nobrega
Francisco G
FG
Nóbrega
Marina Pasetto
MP
Nunes
Diana Noronha
DN
Nunes
Fabio
F
Pandolfi
José Rodrigo
JR
Pardini
Maria Inês M C
MI
Pasini
Fátima Solange
FS
Peres
Tarcisio
T
Rainho
Cláudia Aparecida
CA
dos Reis
Patrícia P
PP
Rodrigus-Lisoni
Flávia Cristina C
FC
Rogatto
Silvia Regina
SR
dos Santos
Andrey
A
dos Santos
Paulo C C
PC
Sogayar
Mar Cleide
MC
Zanelli
Cleslei F
CF
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
D005819:Genetic Markers; D020033:Protein Isoforms; D012333:RNA, Messenger