Near-diploid and near-triploid human sporadic colorectal adenocarcinomas differ for KRAS2 and TP53 mutational status
Article first published online: 28 MAR 2003
Copyright © 2003 Wiley-Liss, Inc.
Genes, Chromosomes and Cancer
Volume 37, Issue 2, pages 207–213, June 2003
How to Cite
Giaretti, W., Venesio, T., Sciutto, A., Prevosto, C., Geido, E. and Risio, M. (2003), Near-diploid and near-triploid human sporadic colorectal adenocarcinomas differ for KRAS2 and TP53 mutational status. Genes Chromosom. Cancer, 37: 207–213. doi: 10.1002/gcc.10203
- Issue published online: 9 APR 2003
- Article first published online: 28 MAR 2003
- Manuscript Accepted: 14 JAN 2003
- Manuscript Received: 18 SEP 2002
- Oncology National Research Project of MIUR-CNR. Grant Number: 02.00273.ST97
- S. Paolo Oncology Program. Grant Number: Special Program art.12 c.2b DL 502/92
Mutations of the KRAS2 protoncogene and inactivation of the TP53 oncosuppressor gene have been suggested to contribute to chromosomal instability (CIN) and aneuploidy in colorectal cancer (CRC). Previous work has also shown that the degree of DNA ploidy [DNA index (DI)], as obtained by flow cytometry in CRC, is non-randomly distributed and, in particular, that DI near-diploid and near-triploid values are well separated by a low-probability valley region. At present, it is not known whether a relationship exists between DI and the mutational status of KRAS2 and TP53. Multiple samples obtained from 35 human sporadic CRCs have been used to provide nuclei suspensions for flow cytometric analysis and sorting of specific DI subpopulations. Sorted nuclei were then used to analyze the high-microsatellite-instability (MSI-H) phenotype and the mutation spectrum of the KRAS2 and TP53 genes. A single MSI-H case was detected. There were 6 DNA diploid (DI = 1) and 29 aneuploid (DI ≠ 1) CRCs, with the DI aneuploid cases non-randomly subdivided in 9 near-diploid (DI ≠ 1 and DI ≤ 1.4), 8 near-triploid (1.4 < DI < 1.6), and 12 high-aneuploid (DI ≥ 1.6) cases. Proximal CRCs were more often DNA diploid and near-diploid than distal ones, and Dukes' C cases were more commonly high-aneuploid than Dukes' B. Moreover, the incidence of mutations of the KRAS2 and TP53 genes was lowest among the DNA near-triploid subpopulations and highest among the near-diploid ones. We suggest that DNA near-diploid and near-triploid subpopulations in human sporadic CRC reflect different genetic mechanisms of CIN and have a potentially different clinical behavior. © 2003 Wiley-Liss, Inc.