The genomic damage estimated by arbitrarily primed PCR DNA fingerprinting is useful for the prognosis of gastric cancer

Abstract

Background & Aims: Genomic instability and the accompanying alteration of cancer genes play a major role in tumorigenesis. We evaluated the prognostic significance in gastric cancer of the degree of accumulation of relative genomic damage, assessed by arbitrarily primed polymerase chain reaction DNA fingerprinting. Methods: Genomic damage was assessed by comparative analysis of paired normal and tumor tissue DNA fingerprints. The total number of alterations, scored as decreases and increases of band intensity with 2 arbitrary primers, were used as an estimation of the genomic damage fraction in 74 primary gastric cancers. Increases in DNA copy number were also analyzed by array comparative genomic hybridization in a subset of 30 cases. Results: The number of altered bands varied among the tumors from none or a few to more than one third of the approximately 40 fingerprint bands. The relative values of genomic damage were consistent with the quantitative chromosomal alterations observed by array comparative genomic hybridization. When the tumors were stratified into 2 groups—above or below the cutoff of 0.22 for average genomic damage fraction—genomic damage fraction was a valuable prognostic indicator regardless of microsatellite instability status. Multivariate Cox analysis showed that the genomic damage fraction was a prognostic indicator, as well as a stage indicator ( P = 0.0189). Survival was significantly diminished in tumors with a genomic damage fraction >0.22 ( P = 0.0009). Moreover, in the 46 curative cases, genomic damage fraction was the only independent factor for predicting survival ( P = 0.0061). Conclusions: Our results indicate that the degree of genomic damage estimated by arbitrarily primed polymerase chain reaction fingerprinting is a useful prognostic indicator for gastric cancer.