Loss of heterozygosity of DPC4 tumor suppressor gene in human sporadic colon cancer.
We investigated the prevalence of DPC4 loss of heterozygosity in sporadic colorectal cancer. Thirty-six cases of human sporadic colon carcinoma and corresponding normal tissue samples were examined to evaluate loss of heterozygosity at the DPC4 tumor suppressor locus using variable nucleotide tandem repeat (VNTR) analysis and three polymorphic markers. From 36 analyzed samples 35 (97%) were heterozygous or informative. Loss of heterozygosity at the DPC4 locus was detected in 18 (51%) of informative tumor DNAs. The DPC4 LOH was more frequent in smaller tumors (<5 cm) than in larger ones. There was no correlation between DPC4 LOH and age or sex of patients. There was a negative correlation between DPC4 LOH and histological grade or Dukes' stage of tumors, but without statistic significance. Observed results are in agreement with the view that malignant progression is consequence of many genetic changes. It can be concluded that inactivation of the DPC4 gene plays a role in a multistep process of outgrowth and progression of colon cancer.
Had ija
M P
MP
Division of Molecular Medicine, Ruder Bosković Insitute, Zagreb, Croatia. mhadzija@rudjer.irb.hr
Kapitanović
S
S
Radosević
S
S
Cacev
T
T
Mirt
M
M
Kovacević
D
D
Cacev
T
T
Hadzija
M
M
Spaventi
R
R
Pavelić
K
K
D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics*
D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators