Identification of genes associated with tumorigenesis and metastatic potential of hypopharyngeal cancer by microarray analysis.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer among men in the developed world. There is a need, for both clinical and scientific reasons, to find markers to identify patients with aggressive disease as early as possible, and to understand the events leading to malignant transformation and susceptibility to metastasis. We report the first large-scale gene expression analysis of a unique HNSCC location, the hypopharynx. Four normal and 34 tumour samples were analysed with 12 600 gene microarrays. Clusters of differentially expressed genes were identified in the chromosomal regions 3q27.3, 17q21.2-q21.31, 7q11.22-q22.1 and 11q13.1-q13.3, which, interestingly, have already been identified by comparative genomic hybridization (CGH) as major regions of gene amplification. We showed that six overexpressed genes (EIF4G1, DVL3, EPHB4, MCM7, BRMS1 and SART1) located in these regions are indeed amplified. We report 119 genes that are highly differentially expressed between 'early' tumours and normal samples. Of these, we validated by quantitative PCR six novel poorly characterized genes. These genes are potential new markers of HNSCC. Comparing patients with relatively nonaggressive and aggressive tumours (without or with clinical evidence of metastasis 3 years after surgery), we identified 164 differentially expressed genes potentially involved in the acquisition of metastatic potential. This study contributes to the understanding of HNSCC, staging patients into prognostic groups and identifying high-risk patients who may benefit from more aggressive treatment.
Cromer
Anne
A
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, BP 10142, 67404 Illkirch cedex, France.
Carles
Annaïck
A
Millon
Régine
R
Ganguli
Gitali
G
Chalmel
Frédéric
F
Lemaire
Frédéric
F
Young
Julia
J
Dembélé
Doulaye
D
Thibault
Christelle
C
Muller
Danièle
D
Poch
Olivier
O
Abecassis
Joseph
J
Wasylyk
Bohdan
B
D000328:Adult; D000368:Aged; D000374:Aggression / Q000523:psychology; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000145:classification / Q000209:etiology* / Q000235:genetics* / Q000523:psychology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D013997:Time Factors