K-RAS point mutation, and amplification of C-MYC and C-ERBB2 in colon adenocarcinoma.
The routine multidisciplinary management of colon cancer is based mainly on tumor staging, histology, grading and vascular invasion. In this approach, important individual information derived from molecular characteristics of the tumor may be missed, especially since significant heterogeneity of molecular aberrations in cancer cells has been observed, and recognition of every of relationships between them may be of value. K-RAS, C-MYC and C-ERBB2 are protooncogenes taking part in carcinogenesis and tumor progression in the colon. They influence cell proliferation, differentiation and survival. K-RAS point mutation, as well as amplification of C-MYC and C-ERBB2 were searched in 84 primary colon adenocarcinomas resected with curative intent. Multiplex polymerase-chain reaction and restriction fragment length polymorphism were performed to assess codon 12 K-RAS point mutation. Amplification of C-MYC and C-ERBB2 genes was evaluated by densitometry after agarose gel separation of the respective multiplex PCR products. No relation was found among mutated and/or amplified genes, and between searched molecular aberrations and pathoclinical features. In multivariate analysis, nodal status appeared to be the only independent prognostic indicator. In colon adenocarcinoma, codon 12 K-RAS point mutation and amplification of C-MYC and C-ERBB2 seem to occur independently in the process of tumor progression. Amplification of C-ERBB2 tends to associate with more advanced stage of disease. Concomitant occurrence of codon 12 K-RAS mutation, C-MYC and C-ERBB2 amplification was of no prognostic value in respect to survival.
Kruszewski
Wiesław
W
Department of Surgical Oncology, Medical University, Gdańsk, Poland. wjkrusz@amg.gda.pl
Kowara
Renata
R
Rzepko
Robert
R
Warezak
Cezary
C
Zieliński
Jacek
J
Gryglewski
Grzegorz
G
Kopacz
Andrzej
A
Jastrzebski
Tomasz
T
Pawełczyk
Tadeusz
T
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D001483:Base Sequence; D003110:Colonic Neoplasms / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2; D016259:Genes, myc; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D017354:Point Mutation