[Allelic loss and down-regulation of FHIT gene expression in esophageal squamous cell carcinoma].
OBJECTIVE
Deletions and translocations involving the short arm of chromosome 3 (3p14) have been observed frequently in esophageal cancer. Fragile histidine triad (FHIT) gene is located in 3p14.2, and its deletion or abnormal expression was found in many kinds of cancers. The study was to investigate the alterations of FHIT gene, and its significance in esophageal squamous cell carcinoma (ESCC).


METHODS
The deletion of FHIT gene in 80 cases of ESCC was evaluated by microsatellite analysis, and the mRNA expression of FHIT gene in 20 cases of ESCC was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR).


RESULTS
Intragenic markers of FHIT gene, D3S3356, D3S3378, and D3S3361, showed homozygous in all samples. D3S1234 and D3S1540, located near FHIT, presented high heterozygosity. In the tested informative cases, loss of heterozygosity (LOH) of D3S1234 was detected in 30 out of 52 tumors (57.69%), and that of D3S1540 was observed in 38 out of 56 carcinomas (67.86%). Reduced expression of FHIT mRNA occurred in 15 of 20 (75.00%) cases, and was often accompanied with LOH. However, the FHIT down-regulation was not always coincident with LOH.


CONCLUSIONS
The abnormal expression of FHIT gene occurred frequently in ESCC. LOH was the main factor leading to down-regulation of FHIT expression. Epigenetic mechanism might be associated with reduced expression of FHIT in a part of ESCC cases.
Liu
Fu-Xing
FX
National key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, PR China.
Huang
Xiao-Ping
XP
Zhao
Chun-Xia
CX
Xu
Xin
X
Han
Ya-Ling
YL
Cai
Yan
Y
Wu
Ren-Liang
RL
Wu
Min
M
Zhan
Qi-Min
QM
Wang
Ming-Rong
MR
D017766:Acid Anhydride Hydrolases / Q000096:biosynthesis / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D002893:Chromosomes, Human, Pair 3; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000099170:Bis(5'-adenosyl)triphosphatase