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


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.


CONCLUSIONS
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.
Petursdottir
Thorgunnur Eyfjord
TE
Department of Pathology, National University Hospital, P.O. Box 1465, IS-121 Reykjavik, Iceland.
Hafsteinsdottir
Sigridur H
SH
Jonasson
Jon G
JG
Moller
Pall H
PH
Thorsteinsdottir
Unnur
U
Huiping
Chen
C
Egilsson
Valgardur
V
Ingvarsson
Sigurdur
S
D017766:Acid Anhydride Hydrolases; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D015996:Survival Rate; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D005819:Genetic Markers; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase