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  • Title: K-ras-2 G-C and G-T transversions correlate with DNA aneuploidy in colorectal adenomas.
    Author: Giaretti W, Pujic N, Rapallo A, Nigro S, Di Vinci A, Geido E, Risio M.
    Journal: Gastroenterology; 1995 Apr; 108(4):1040-7. PubMed ID: 7698570.
    Abstract:
    BACKGROUND/AIMS: K-ras-2 mutations and DNA content heterogeneity represent early events of human colorectal tumor progression. The aim of the study was to investigate if specific K-ras-2 mutations in 58 human sporadic adenomas were correlated with DNA aneuploidization and cell proliferation. METHODS: Multiparameter flow cytometry, based on scatter parameters and DNA content, was performed using 4,6-diamidino-2-phenilindole-2-hydrochloride-stained nuclei obtained from adenoma fragments with either mild-moderate or severe dysplasia. K-ras-2 polymerase chain reaction and spectrum analysis were performed using sorted DNA specific epithelial subclones. RESULTS: We detected six G-A transitions, and four G-C and two G-T transversions. The DNA aneuploid subclones were 25 with DNA index values in the near diploid region (DNA index < 1.3) for the vast majority of cases (80%). DNA aneuploidy among the mutated adenomas with G-A transitions was 1 of 6 (17%) and 6 of 6 (100%) among G-C and G-T transversions. Although DNA aneuploidy and high S-phase values were also present among K-ras-2 wild-type adenomas, their statistical associations with K-ras-2 status were P < 0.005 and P < 0.05, respectively. CONCLUSIONS: The present series of sporadic colorectal adenomas indicates that codon 12 G-C and G-T K-ras-2 transversion mutations and DNA aneuploidy are correlated. The underlying mechanisms that explain such association remain to be investigated.
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