Loss of heterozygosity at the FHIT gene in different solid human tumours and its association with survival in colorectal cancer patients

• Main Authors: Sigurður Ingvarsson 1956-, Þórgunnur Eyfjörð Pétursdóttir 1970-, Sigríður Harpa Hafsteinsdóttir 1976-, Jón Gunnlaugur Jónasson 1956-, Páll Helgi Möller 1960-, Unnur Þorsteinsdóttir 1958-, Huiping Chen, 1965-, Valgarður Egilsson 1940-
• Other Authors: Háskóli Íslands
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2002
• Subjects: Krabbamein; Iceland
• Online Access: http://hdl.handle.net/1946/21898

BACKGROUND: Genomic alterations and abnormal expression of the FHIT gene have been reported for a number of cancers. FHIT encompasses FRA3B, the most common fragile site in the human genome, and is suggested to be a candidate tumour suppressor gene. MATERIALS AND METHODS: We analysed and compared the loss of heterozygosity (LOH) pattern in 397 solid human tumours from 9 different locations, using four polymorphic microsatellite markers within the gene (D3S1234, D3S1300, D3S2757 and D3S4260), and two markers (D3S1313 and D3S1600) flanking the gene. In addition, we tested whether there was an association between FHIT LOH and overall patient survival in colorectal cancer. RESULTS: LOH at the FHIT gene affecting at least one of the investigated markers was detected in 166 out of 332 informative tumours, or 50%. The highest detected LOH was in lung tumours (66%) while the lowest was in thyroid and endometrium tumours, (30% and 31%, respectively). Breakpoints were found inside the gene in all tumour types in 12-80% of the tumours with FHIT LOH depending on tumour type, and up to 41% could additionally be located adjacent to the 3' or 5' end of the FHIT gene. Thus we were able to locate breakpoints within or in the vicinity of the FHIT gene in 25-100% of different tumours with LOH. Although not statistically significant, we observed a trend towards a poorer survival of patients with FHIT LOH versus those with retention of heterozygosity. CONCLUSION: Based on our results, LOH of the FHIT gene is a common event in all tumour types analysed with a possible association with poorer survival in colorectal cancer patients. LOH at all markers analysed was, in most of the tumour types, a more common pattern of alterations than breakpoints. This work was financially supported by the Science fund of the Icelandic Cancer Society, the Research fund of the University of Iceland and the Science fund of the University Hospital of Iceland.