Frameshift mutation of the STK11 gene in a sporadic gastrointestinal cancer with microsatellite instability

Germline mutations of the STK11 gene lead to emergence of hamartomas in the gastrointestinal tract of patients with Peutz-Jeghers syndrome, who bear a n increased risk of malignancies of the gastrointestinal tract, genital tra ct, and other organs. We analyzed 80 sporadic colorectal cancers, six small -intestinal cancers, and 40 gastric cancers for somatic mutations of STK11 by SSCP methods. Among them only one colorectal cancer, which showed a phen otype of microsatellite instability, was found to possess a deleterious mut ation in this gene, a frameshift involving deletion of one base at codons 2 79-281, This region of the gene contains a mononucleotide-repeat sequence, CCCCCC, The other allele of STK11 had been lost in this tumor. If the STK11 gene is one of the mutational targets of microsatellite instability, its i nactivation may be associated with tumor development in a small proportion of colorectal cancers.