FREQUENT SOMATIC MUTATIONS IN SERINE THREONINE KINASE-11 PEUTZ-JEGHERS-SYNDROME GENE IN LEFT-SIDED COLON-CANCER/

We analyzed somatic mutation and loss of heterozygosity (LOH) in the s erine/threonine kinase II (STK11)/Peutz-Jeghers syndrome gene in 49 co lorectal tumors in three different stages of a dysplasia-carcinoma seq uence. We detected LOH in 10 of 19 (52.6%) informative colorectal canc ers at loci D19S886 and/or D19S883, but no LOH was observed in 25 info rmative adenomas. We detected a total of 9 somatic mutations [7 of 13 (53.8%) left-sided colon cancers and 2 of 7 (28.6%) left-sided adenoma s with high-grade dysplasia], but no mutations were detected in right- sided colon tumors. Of the nine mutations, one was a frameshift mutati on (the same mutation detected in Peutz-Jeghers syndrome family previo usly), and the other eight were missense mutations. This results indic ate that STK11 is a tumor suppressor gene and that genetic changes of STK11 play an important role in left-sided colon cancer carcinogenesis .