Journal of Clinical Oncology, Vol 15, 3230-3240, Copyright © 1997 by American Society of Clinical Oncology
Assessment of genomic damage in colorectal cancer by DNA fingerprinting: prognostic applications
R Arribas, G Capella, S Tortola, L Masramon, WE Grizzle, M Perucho and MA Peinado
Institut de Recerca Oncologica, Hospital Duran i Reynals, Barcelona, Spain.
PURPOSE: Here we evaluate the prognostic significance of the relative value
of genomic damage assessed by DNA fingerprinting in colorectal cancer.
MATERIALS AND METHODS: Sixty-three tumor and paired normal mucosa samples
were included in the study. Genomic damage was assessed by comparative
analysis of paired normal and tumor tissue DNA fingerprints by the
arbitrarily primed polymerase chain reaction (AP- PCR). Decreases and
increases of intensity in bands were computed and referred to the total
number of visualized bands per case. An index reflecting the genomic damage
fraction (GDF), with separated values for losses and gains, was obtained
for each tumor. This index was used to determine molecular and
clinicopathologic correlates after exclusion of eight cases displaying
microsatellite instability. RESULTS: Fifty-five cases were considered for
the statistical analysis. The average fraction of altered bands per tumor
was 0.287+/-0.121. When losses and gains were computed separately, the
average fraction of changes was 0.126+/-0.113 and 0.161+/-0.120,
respectively. Tumors lacking a ras mutation showed an increased GDF,
primarily because of a higher fraction of gains. Tumors that were at
advanced Dukes' stages and that were poorly differentiated also displayed a
higher GDF. Finally, disease-free survival was significantly diminished in
tumors with a GDF greater than 0.314 (P < .001). The prognostic
significance of the GDF was independent of Dukes' stage (Cox multivariate
analysis, P = .005). CONCLUSION: The degree of genomic damage assessed by
unbiased DNA fingerprinting correlates with genotypic, phenotypic, and
clinical variables in colorectal carcinoma and may be useful in assessing
prognosis in colorectal cancer.
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