K-ras-2 G-C and G-T transversions correlate with DNA aneuploidy in colorectal adenomas.
OBJECTIVE
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.
Giaretti
W
W
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Pujic
N
N
Rapallo
A
A
Nigro
S
S
Di Vinci
A
A
Geido
E
E
Risio
M
M
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D001483:Base Sequence; D003062:Codon; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D016196:S Phase
D003062:Codon; D004273:DNA, Neoplasm