Molecular analysis of the FHIT gene in human prostate cancer.
A variety of studies suggest that the FHIT gene, which encompasses the fragile site at 3p14.2, is a candidate tumor suppressor gene in several forms of human cancer. To determine whether the FHIT gene is altered in prostate carcinomas, we examined 15 prostate tumors, four normal prostate tissue specimens and RNA from a pool of 62 normal human prostate tissues (Clontech) for the integrity of FHIT transcripts, using a robust single-stage PCR and a nested PCR method. In each case a major FHIT-specific full-length product was observed. Additional aberrantly sized products, which were more numerous in the nested PCR strategy, were present at a far lower level than the full-length transcripts in 14 of 15 tumors, three of four normal human prostate tissues and in the pooled normal prostate RNA. Sequence analysis revealed that these aberrant products corresponded to alternatively spliced FHIT transcripts, which were neither more numerous nor more prominent in the tumors than in the normal prostate specimens. Deletion at the FHIT locus was also evaluated by using three intragenic polymorphic markers (D13S1481, D3S1300, and D3S1234). Allelic loss was observed in two tumors, but these genomic alterations did not correspond to the aberrant FHIT transcripts. DNA analysis, furthermore, suggested that the tumor heterogeneity was not a likely explanation for presence of normal and alternatively spliced FHIT transcripts in the prostate tumors. In conclusion, we detected neither frequent loss of heterozygosity nor tumor specific transcripts of the FHIT gene in human prostate cancer.
Latil
A
A
Laboratoire d'Oncogénétique, Centre René Huguenin, St-Cloud, France.
Bièche
I
I
Fournier
G
G
Cussenot
O
O
Pesche
S
S
Lidereau
R
R
D017766:Acid Anhydride Hydrolases; D000595:Amino Acid Sequence; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D002893:Chromosomes, Human, Pair 3; D004273:DNA, Neoplasm / Q000032:analysis; D005819:Genetic Markers; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D014158:Transcription, Genetic; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D004273:DNA, Neoplasm; D005819:Genetic Markers; D009363:Neoplasm Proteins; D011506:Proteins; D000099170:Bis(5'-adenosyl)triphosphatase