Simultaneous mutations in K-ras and TP53 are indicative of poor prognosis in sporadic colorectal cancer.
Despite the fact that the mutations in K-ras codon 12 and TP53 are common abnormalities in colorectal cancer, the determination of K-ras mutation combined with TP53 gene mutation, with diagnostic and prognostic purposes is still controversial. We have analyzed K-ras and TP53 mutations in 77 sporadic colorectal adenocarcinomas by means of polymerase chain reaction and sequencing. We observed a negative correlation between both K-ras and TP53 mutations. Patients with mutations in K-ras but not in TP53 exhibited worse survival rates than those with mutations in TP53 and not in K-ras. Moreover, we found the worst outcome in patients with mutations in both K-ras and TP53. These results may relate to the previously published data about primary human and rodent cells, in which transformation by Ras require either a cooperating oncogene or the inactivation of tumor suppressors such as p53 or p16. In conclusion, simultaneous mutations in K-ras and TP53 are indicative of a worse prognosis in sporadic colorectal cancer.
González-Aguilera
Juan J
JJ
Unidad de Genética, Departamento de Biología, Universidad Autónoma de Madrid, Madrid, Spain.
Oliart
Soledad
S
Azcoita
Mariano Moreno
MM
Fernández-Peralta
Antonia M
AM
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis