Genome-wide profiling of oral squamous cell carcinoma.
Oral squamous cell carcinoma (OSCC) is a common malignancy, the incidence of which is particularly high in some Asian countries due to the geographically linked areca quid (AQ) chewing habit. In this study, array-based comparative genomic hybridization was used to screen microdissected OSCCs for genome-wide alterations. The highest frequencies of gene gain were detected for TP63, Serpine1, FGF4/FGF3, c-Myc and DMD. The highest frequencies of deletion were detected for Caspase8 and MTAP. Gained genes, classified by hierarchical clustering, were mainly on 17q21-tel; 20q; 11q13; 3q27-29 and the X chromosome. Among these, gains of EGFR at 7p, FGF4/FGF3, CCND1 and EMS1 at 11q13, and AIB1 at 20q were significantly associated with lymph node metastasis. The genomic profiles of FHIT and EXT1 in AQ-associated and non-AQ-associated OSCCs exhibited the most prominent differences. RT-PCR confirmed the significant increase of TP63 and Serpine1 mRNA expression in OSCC relative to non-malignant matched tissue. A significant increase in Serpine1 immunoreactivity was observed from non-malignant matched tissue to OSCC. However, there was no correlation between the frequent genomic loss of Caspase 8 and a significant decrease in Caspase8 expression. These data demonstrate that genomic profiling can be useful in analysing pathogenetic events involved in the genesis or progression of OSCC.
Chen
Yann-Jang
YJ
Department of Life Science, National Yang-Ming University, Taipei, Taiwan.
Lin
Shu-Chun
SC
Kao
Tsai
T
Chang
Che-Shoa
CS
Hong
Pei-She
PS
Shieh
Tzong-Ming
TM
Chang
Kuo-Wei
KW
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D053181:Caspase 8; D020169:Caspases / Q000032:analysis; D016000:Cluster Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D051518:Fibroblast Growth Factor 3; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000032:analysis; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008207:Lymphatic Metastasis / Q000235:genetics; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D004273:DNA, Neoplasm; C496444:FGF3 protein, human; C496445:FGF4 protein, human; D051518:Fibroblast Growth Factor 3; D051519:Fibroblast Growth Factor 4; D009363:Neoplasm Proteins; D017395:Plasminogen Activator Inhibitor 1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D005346:Fibroblast Growth Factors; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases