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

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.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Giaretti W,Pujic N,Rapallo A,Nigro S,Di Vinci A,Geido E,Risio M

doi

10.1016/0016-5085(95)90201-5

subject

Has Abstract

pub_date

1995-04-01 00:00:00

pages

1040-7

issue

4

eissn

0016-5085

issn

1528-0012

pii

0016-5085(95)90201-5

journal_volume

108

pub_type

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