Clinicopathologic features and FHIT gene expression in sporadic colorectal adenocarcinomas.
BACKGROUND
The putative tumour suppressor gene FHIT (fragile histidine triad) spans the common fragile site FRA3B, which is highly susceptible to breaks and deletions induced by genotoxic agents. Tumours associated with exposure to carcinogens, such as colorectal adenocarcinomas, should be particularly susceptible to alterations in the FHIT gene. We studied the frequency of FHIT alterations and their correlations with clinicopathologic features in sporadic colon carcinomas.


METHODS
FHIT expression was investigated by reverse transcription polymerase chain reaction in 56 primary sporadic colorectal carcinomas. The same tumours and matched normal tissues were also investigated for loss of heterozygosity by using two markers located inside the FHIT gene.


RESULTS
Twenty-nine of 56 tumours (51.8%) expressed aberrant FHIT transcripts. Four tumours had absence or nearly undetectable levels of the normal-sized FHIT transcript. Sequencing analysis of the altered transcripts showed FHIT mRNA lacking one or more exons, more frequent deletions of exons 4-5-6 or 4-5-6-7-8. At the genomic level 46.4% (13 of 28) of the cases showed alterations involving FHIT locus. We did not find any correlation between FHIT gene alterations and clinicopathologic characteristics of the tumours.


CONCLUSIONS
Since the FHIT gene is frequently altered, its role in the molecular pathogenesis of sporadic colon carcinoma deserves further investigation.
Dept of Pharmacology, University of Florence, Florence, Italy.
C
C
Luceri
F
F
Guglielmi
C
C
De Filippo
G
G
Caderni
E
E
Mini
A
A
Biggeri
C
C
Napoli
F
F
Tonelli
F
F
Cianchi
P
P
Dolara
D017766:Acid Anhydride Hydrolases; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015870:Gene Expression; D016147:Genes, Tumor Suppressor / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D011336:Probability; D011506:Proteins / Q000235:genetics*; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D004273:DNA, Neoplasm; D005819:Genetic Markers; D009363:Neoplasm Proteins; D011506:Proteins; D012334:RNA, Neoplasm; D000099170:Bis(5'-adenosyl)triphosphatase