K-ras-2 G-C and G-T transversions correlate with DNA aneuploidy in colorectal adenomas

Walter Giaretti, Natalija Pujic, Anna Rapallo, Stefano Nigro, Angela di Vinci, Elio Geido, Mauro Risio

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1040-1047
Number of pages8
JournalGastroenterology
Volume108
Issue number4
DOIs
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Gastroenterology

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    Giaretti, W., Pujic, N., Rapallo, A., Nigro, S., di Vinci, A., Geido, E., & Risio, M. (1995). K-ras-2 G-C and G-T transversions correlate with DNA aneuploidy in colorectal adenomas. Gastroenterology, 108(4), 1040-1047. https://doi.org/10.1016/0016-5085(95)90201-5