Multiple molecular alterations of FHIT in betel-associated oral carcinoma.
To determine the alterations of the FHIT (fragile histidine triad) gene in oral squamous cell carcinoma (OSCC), this study examined mutation, promoter methylation, mRNA transcription, and protein expression of FHIT in OSCC associated mostly with the use of betel and/or tobacco. Analyses of the coding exons (exons 5-9) identified a deletion of one base in intron 4 in one tumour and a deletion of exon 7 in two tumours. Using bisulphite genomic sequencing, 28% of the informative subjects exhibited promoter methylation. An aberrant FHIT transcript spanning from exon 3 to exon 10, which was verified by RT-PCR analysis, was identified in 36% of the OSCC subjects, 50% of the oral pre-invasive lesions, and 5% of the non-cancerous match tissue. An abnormal immunohistochemical level of Fhit was detected in 41% of OSCC subjects. A statistically significant association was found between aberrant transcription of the FHIT gene and an abnormal level of Fhit immunoreactivity. The results indicated that alteration of FHIT is a frequent occurrence in OSCC and thus suggests that the aberrance in FHIT transcription could be an early event of oral carcinogenesis.
Chang
Kuo-Wei
KW
Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan, ROC 112.
Kao
Shou-Yen
SY
Tzeng
Reuo-Jar
RJ
Liu
Chung-Ji
CJ
Cheng
Ann-Joy
AJ
Yang
Shun-Chun
SC
Wong
Yong-Kie
YK
Lin
Shu-Chun
SC
D017766:Acid Anhydride Hydrolases; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001114:Areca; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000235:genetics; D016022:Case-Control Studies; D004247:DNA / Q000032:analysis; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology* / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011230:Precancerous Conditions / Q000209:etiology* / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D004247:DNA; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000099170:Bis(5'-adenosyl)triphosphatase