help button home button Am J Pathol R & D Systems
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Giaretti, W.
Right arrow Articles by Rossini, F. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Giaretti, W.
Right arrow Articles by Rossini, F. P.
(American Journal of Pathology. 1998;153:1201-1209.)
© 1998 American Society for Investigative Pathology

Regular Articles

Specific K-ras2 Mutations in Human Sporadic Colorectal Adenomas Are Associated with DNA Near-Diploid Aneuploidy and Inhibition of Proliferation

Walter Giaretti* , Anna Rapallo* , Elio Geido* , Andrea Sciutto* , Franco Merlo{dagger} , Mauro Risio{ddagger} and Francesco P. Rossini§

From the Laboratory of Biophysics-Cytometry* and Department of Environmental Epidemiology and Biostatistics,{dagger} National Institute for Cancer Research and Treatment, Candiolo, Genoa, and Departments of Pathology{ddagger} and Gastroenterology,§ S. Giovanni Vecchio Hospital, Turin, Italy

Recent studies indicate that p21ras proteins mediate their multiple cell functions through interactions with multiple effectors and that the number of new effectors is growing. We recently reported that K-ras2 mutations in human colorectal adenomas were associated with chromosome instability and proliferation changes. In the present study, we extend these previous observations. Hereditary and multiple (n >= 5) adenomas and adenomas with early cancer were excluded. Dysplasia was moderate in 91 cases and high in 25, and the median adenoma size was 1.5 cm. K-ras2 spectrum analysis was done by sequence-specific oligonucleotide hybridization using nuclear suspensions provided by analysis and sorting of multiparameter flow cytometry. In particular, tissue inflammatory cells were separated for DNA diploid tumors, whereas DNA aneuploid epithelial subclones were analyzed separately. K-ras2 mutations and DNA aneuploidy were both detected in 29 of 116 (25%) cases. DNA aneuploid index was in the near-diploid region in the majority of cases. DNA aneuploidy was strongly associated with G->C/T transversions. An association was also found between low S-phase values and G->A transitions. These findings were confirmed using multivariate logistic regression analysis to account for the effects of size, dysplasia, site, type, age, and sex. These data suggest that specific K-ras2 mutations in a subgroup of human sporadic colorectal adenomas play a role in chromosome instability and, contrary to expectations, are associated with inhibition of proliferation.




This article has been cited by other articles:


Home page
 GutHome page
H J N Andreyev, R Benamouzig, M Beranek, P Clarke, D Cunningham, A R Norman, W Giaretti, A F P M de Goeij, B J Iacopetta, E Jullian, et al.
Mutant K-ras2 in serum
Gut, June 1, 2003; 52(6): 915 - 916.
[Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1998 by the American Society for Investigative Pathology.