High frequency of LOH, MSI and abnormal expression of FHIT in gastric cancer
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Bergthorsson, J T
Jonasson, J G
MetadataShow full item record
CitationEur. J. Cancer. 2002, 38(5):728-35
AbstractThe FHIT gene is a putative tumour suppressor gene. In this study, we analysed a set of 50 gastric tumours for alterations of FHIT, and found 38 of 45 tumours (84%) exhibiting loss of heterozygosity (LOH) within the FHIT gene. We used both nested Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and single step RT-PCR to analyse the FHIT transcripts and found 34 of 39 (87%) tumours and seven of the 11 (64%) corresponding non-cancerous tissues showed low or aberrant expression of FHIT mRNA and the appearance of the aberrant FHIT transcripts depended on the conditions of the RT-PCR. In these aberrant transcripts, frequent deletions and/or insertions were detected by direct sequencing. All breakpoints for deletions and insertions were at splicing sites. All insertions came from the adjacent introns, whose appearance was completely in accordance with the 'GU-AG' rule for pre-mRNA splicing. It may be suggested that an alternative splicing mechanism functions in the formation of these aberrant transcripts. The fragile nature of FRA3B within the FHIT gene could be responsible for the formation of the aberrant mRNA. Negative or reduced Fhit expression was detected in 39 of 50 tumours (78%). Moreover, an association was found between abnormal Fhit expression and positive node status (P=0.012). Thirteen of 48 tumours (27%) displayed microsatellite instability (MSI), among which 10 tumours also showed MSI within the FHIT gene. Furthermore, we detected an association between MSI and negative node status (P=0.02). We conclude that the abnormalities of FHIT, presumably associated with the unstable nature of FRA3B within the FHIT gene, are involved in the carcinogenesis of gastric cancer, and lack of mismatch repair (MMR) could possibly promote its alteration in a subset of gastric tumours.
DescriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field
- Altered expression of the fragile histidine triad gene in primary gastric adenocarcinomas.
- Authors: Lee SH, Kim WH, Kim HK, Woo KM, Nam HS, Kim HS, Kim JG, Cho MH
- Issue date: 2001 Jun 15
- FHIT and TSG101 in thyroid tumours: aberrant transcripts reflect rare abnormal RNA processing events of uncertain pathogenetic or clinical significance.
- Authors: McIver B, Grebe SK, Wang L, Hay ID, Yokomizo A, Liu W, Goellner JR, Grant CS, Smith DI, Eberhardt NL
- Issue date: 2000 Jun
- Aberrant splicing of FHIT transcripts in human gastric cancer cell lines.
- Authors: Lee SH, Kim HY, Kim TJ, Park HK, Kim WH, Woo KM, Cho MH
- Issue date: 2002
- Loss of heterozygosity and microsatellite instabilities of fragile histidine triad gene in gastric carcinoma.
- Authors: Xiao YP, Wu DY, Xu L, Xin Y
- Issue date: 2006 Jun 21
- FHIT and FRA3B 3p14.2 allele loss are common in lung cancer and preneoplastic bronchial lesions and are associated with cancer-related FHIT cDNA splicing aberrations.
- Authors: Fong KM, Biesterveld EJ, Virmani A, Wistuba I, Sekido Y, Bader SA, Ahmadian M, Ong ST, Rassool FV, Zimmerman PV, Giaccone G, Gazdar AF, Minna JD
- Issue date: 1997 Jun 1