We previously reported the occurrence of novel dinucleotide mutations of the 
K-RAS gene (KRAS2) in 2% of pancreatic tumors sampled, but it remained unknown 
whether these were functional mutations that convert the proto-oncogene to an 
oncogene, or unselected mutations that might inactivate protein function. In the 
current study, the functionality of these rare mutations was quantitated via a 
mitogen-activated protein kinase (MAPK) pathway-specific transactivational 
reporter system. Pathway activation by dinucleotide mutant proteins was 
comparable to that of the common G12V mutant K-Ras protein. Current 
allele-specific technologies often employed to detect K-RAS mutations in 
clinical tumor samples produce false results when dinucleotide mutations are 
present. Therefore, it is advisable to consider dinucleotide KRAS2 mutants in 
the strategic design of mutational screens used to assay clinical tumor samples. 
Hum Mutat 18:357, 2001.