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Gastric cancer and precancerous lesions of FHIT gene and protein expression studies

Author: YouSiHong
Tutor: LiuPing
School: Nanjing Medical University
Course: Department of Medical Oncology
Keywords: gastric cancer atypical hyperplasia intestinal metaplasia FHIT gene LOH Fhit Expression
CLC: R735.2
Type: Master's thesis
Year: 2005
Downloads: 82
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Abstract

Background and Objective. Although gastric cancer is mainly caused by gene abnormalities, the exact mechanism of the disease is not completely clear. Searching for gene alterations in the tumorigenesis of gastric cancer can help clarifying the mechanism and finding specific way of early diagnosis of the disease. Recently, a gene called fragile histidine triad attracts people’s attention. The gene is regarded as tumour suppressor gene. But the relationship between abnormalities of FHIT gene or Fhit protein expression and the tumorigenesis of gastric cancer remains uncertain. In this study, the role of FHIT gene and protein abnormalities in the carcinogenesis of gastric cancer was analyzed through investigation of deletions and mutations of the gene and alterations of Fhit protein expression in gastric cancer, atypical hyperplasia and intestinal metaplasia samples.Methods. The allelic deletions and mutations of exon 5,8 of FHIT gene and microsatellites loci D3S1300, D3S1234, D3S1312, D3S1313 were analyzed in 36 gastric cancer samples and their corresponding normal tissues by PCR-SSCP. The LOH rate of microsatellites loci D3S1234 and D3S1300 of the gene were analyzed in 42 gastric cancer, 44 atypical hyperplasia and 51 intestinal metaplasia samples and their corresponding normal tissues by PCR. The expression of Fhit protein was observed in 30 gastric cancer and their corresponding atypical hyperplasia tissuesadjacent to tumours, 33 intestinal metaplasia and 14 normal controlsamples.Results(1) Deletion of exon 5 was observed in 2 out of 36 tumor samples, and no deletion of exon 8 was found; The LOH (Loss of heterozygosity) rate and MSI (microsatellite instability) rate at D3S1300 locus were 25%(7/28) and 22.2%(8/36), respectively; The LOH rate and MSI rate at D3S1234 were 31%(9/29) and 13.9%(5/36), respectively; No mutation was found at exon 5,8 of the gene and microsatellites loci D3S1300, D3S1234, D3S1312, D3S1313 by SSCP analysis.(2) The LOH rate of gastric cancer, atypical hyperplasia and intestinal metaplasia were 32.4%(11/34), 28.6%(10/35), 10%(4/40) at D3S1234 locus, and were 30.3% (10/33), 32.4% (11/34), 7.7% (3/39) at D3S1300 locus, respectively; The LOH rate of gastric cancer and atypical hyperplasia at D3S1234 and D3S1300 loci are higher than that of intestinal metaplasia.(3) No negative Fhit protein Expression was detected in normal control samples. The rate of negative Fhit protein Expression in gastric cancer, atypical hyperplasia and intestinal metaplasia were 14/30 (46.7 % X 12/30 (40% ), 3/33 (9.1% ), respectively. The rate of negative Fhit protein Expression in gastric cancer and atypical hyperplasia are higher than that of intestinal metaplasia ( P < 0.01 ) .(4) No statistical difference was found between gastric cancer with and without lymph node metastasis or between gastric cancer of early stage and progressive stage in Fhit protein Expression. The rate of negative Fhit protein Expression in gastric cancer of high, moderate and low differentiation were 18.2% (2/11) , 44.4% ( 4/9) and 80% ( 8/10) , respectively. The rate of negative Fhit protein Expression in low differentiated gastric cancer is higher than that in high-differentiated gastric cancer.Conclusion1. The rate of deletion and mutation of exon 5,8 of FHIT gene was low in gastric cancer, the role of the deletion and mutation of exon 5,8 of the gene in the tumorigenesis of gastric cancer need more research;2. The rate of LOH and MSI at D3S1300 and D3S1234 loci are relatively high in gastric cancer, which suggest LOH and MSI of FHIT gene may play some role in the tumorigenesis of gastric cancer in some extent.3. The loss of heterozygosity of FHIT gene may be an early event in the tumorigenesis of gastric cancer. Detecting LOH probably may be one of the useful ways in screening and early diagnosis of gastric cancer.4. Detecting Fhit protein Expression status may be useful in

Gastric cancer and precancerous lesions of FHIT gene and protein expression studies

Abstract

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