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K-ras and p16 aberrations confer poor prognosis in human colorectal cancer.
J Clin Oncol. 2001 Jan 15; 19(2):299-304.JC

Abstract

PURPOSE

Mutations in the K-ras gene are frequent in human cancer. ras activation in primary cells results in a cellular senescence phenotype that is precluded by inactivation of p16. At the clinical level, this may imply a differential behavior for tumors with alternative or cooperative activation of K-ras function and impairment of p16 pathways.

PATIENTS AND METHODS

We have determined the presence of mutations in the K-ras gene and the methylation status of p16 promoter in a series of 119 prospectively collected colorectal carcinomas. p53 mutations and p14 alternative reading frame methylation status were also assessed. Associations with survival were investigated.

RESULTS

K-ras mutations were present in 44 (38%) of 115 cases, and p16 methylation was present in 42 (37%) of 113 cases. p53 mutations were detected in 50% (56 of 115) and p14 methylation in 29% (32 of 112) of cases. K-ras and p16 alterations were independent genetic events. Presence of K-ras or p16 genetic alterations (analyzed independently) was associated with shorter survival, although differences were not statistically significant. Cox analysis of the two variables combined showed a diminished survival as the results of an interaction between p16 and K-ras. Alternative alteration of K-ras and p16 genes was an independent prognostic factor in human colorectal cancer in univariate and multivariate analysis. Differences were maintained when cases undergoing radical surgery and without distant metastases were considered.

CONCLUSION

These results suggest that the combined K-ras and p16 analyses may be of prognostic use in human colorectal cancer.

Authors+Show Affiliations

Johns Hopkins Oncology Center, Baltimore, MD, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11208819

Citation

Esteller, M, et al. "K-ras and P16 Aberrations Confer Poor Prognosis in Human Colorectal Cancer." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 19, no. 2, 2001, pp. 299-304.
Esteller M, González S, Risques RA, et al. K-ras and p16 aberrations confer poor prognosis in human colorectal cancer. J Clin Oncol. 2001;19(2):299-304.
Esteller, M., González, S., Risques, R. A., Marcuello, E., Mangues, R., Germà, J. R., Herman, J. G., Capellà, G., & Peinado, M. A. (2001). K-ras and p16 aberrations confer poor prognosis in human colorectal cancer. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 19(2), 299-304.
Esteller M, et al. K-ras and P16 Aberrations Confer Poor Prognosis in Human Colorectal Cancer. J Clin Oncol. 2001 Jan 15;19(2):299-304. PubMed PMID: 11208819.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - K-ras and p16 aberrations confer poor prognosis in human colorectal cancer. AU - Esteller,M, AU - González,S, AU - Risques,R A, AU - Marcuello,E, AU - Mangues,R, AU - Germà,J R, AU - Herman,J G, AU - Capellà,G, AU - Peinado,M A, PY - 2001/2/24/pubmed PY - 2001/4/3/medline PY - 2001/2/24/entrez SP - 299 EP - 304 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 19 IS - 2 N2 - PURPOSE: Mutations in the K-ras gene are frequent in human cancer. ras activation in primary cells results in a cellular senescence phenotype that is precluded by inactivation of p16. At the clinical level, this may imply a differential behavior for tumors with alternative or cooperative activation of K-ras function and impairment of p16 pathways. PATIENTS AND METHODS: We have determined the presence of mutations in the K-ras gene and the methylation status of p16 promoter in a series of 119 prospectively collected colorectal carcinomas. p53 mutations and p14 alternative reading frame methylation status were also assessed. Associations with survival were investigated. RESULTS: K-ras mutations were present in 44 (38%) of 115 cases, and p16 methylation was present in 42 (37%) of 113 cases. p53 mutations were detected in 50% (56 of 115) and p14 methylation in 29% (32 of 112) of cases. K-ras and p16 alterations were independent genetic events. Presence of K-ras or p16 genetic alterations (analyzed independently) was associated with shorter survival, although differences were not statistically significant. Cox analysis of the two variables combined showed a diminished survival as the results of an interaction between p16 and K-ras. Alternative alteration of K-ras and p16 genes was an independent prognostic factor in human colorectal cancer in univariate and multivariate analysis. Differences were maintained when cases undergoing radical surgery and without distant metastases were considered. CONCLUSION: These results suggest that the combined K-ras and p16 analyses may be of prognostic use in human colorectal cancer. SN - 0732-183X UR - https://www.unboundmedicine.com/medline/citation/11208819/K_ras_and_p16_aberrations_confer_poor_prognosis_in_human_colorectal_cancer_ L2 - http://ascopubs.org/doi/full/10.1200/JCO.2001.19.2.299?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -