K-ras mutations and RASSF1A promoter methylation in colorectal cancer.
Human cancer is characterized by genetic and epigenetic alterations. In this study we provide evidence for the interruption of Ras signaling in sporadic colorectal cancer (CRC) by either genetic activation of the K-ras oncogene or epigenetic silencing of the putative tumor suppressor gene RASSF1A. Paraffin embedded tumor tissue samples from 222 sporadic CRC patients were analysed for K-ras codon 12 and codon 13 activating mutations and RASSF1A promoter hypermethylation. Overall, K-ras mutations were observed in 87 of 222 (39%) and RASSF1A methylation was observed in 45 of 222 (20%) of CRCs. Mutation of K-ras alone was detected in 76 of 222 (34%) CRCs. RASSF1A promoter methylation with wild-type K-ras was observed in 34 of 222 (15%) CRCs. In 101 of 222 (46%) CRCs neither K-ras mutations nor RASSF1A methylation was observed and 11 of 222 (5%) CRCs showed both K-ras mutations and RASSF1A methylation. These data show that the majority of the studied CRCs with K-ras mutations lack RASSF1A promoter methylation, an event which occurs predominantly in K-ras wild-type CRCs (P=0.023, Chi-square test).
van Engeland
Manon
M
Department of Pathology, University Maastricht, P.O. Box 616 6200 MD Maastricht, The Netherlands.
Roemen
Guido M J M
GM
Brink
Mirian
M
Pachen
Marco M M
MM
Weijenberg
Matty P
MP
de Bruïne
Adriaan P
AP
Arends
Jan-Willem
JW
van den Brandt
Piet A
PA
de Goeij
Anton F P M
AF
Herman
James G
JG
D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D016147:Genes, Tumor Suppressor; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D009363:Neoplasm Proteins; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins