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 serine/threonine kinase 11 (STK11)/Peutz-Jeghers syndrome gene in 49 colorectal tumors in three different stages of a dysplasia-carcinoma sequence. We detected LOH in 10 of 19 (52.6%) informative colorectal cancers at loci D19S886 and/or D19S883, but no LOH was observed in 25 informative 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 adenomas with high-grade dysplasia], but no mutations were detected in right-sided colon tumors. Of the nine mutations, one was a frameshift mutation (the same mutation detected in Peutz-Jeghers syndrome family previously), and the other eight were missense mutations. This results indicate that STK11 is a tumor suppressor gene and that genetic changes of STK11 play an important role in left-sided colon cancer carcinogenesis.

[1]  H. S. Kim,et al.  A distinct region of chromosome 19p13.3 associated with the sporadic form of adenoma malignum of the uterine cervix. , 1998, Cancer research.

[2]  M. Stratton,et al.  A serine/threonine kinase gene defective in Peutz–Jeghers syndrome , 1998, Nature.

[3]  J. Nezu,et al.  Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. , 1998, Nature genetics.

[4]  J. Nezu,et al.  Peutz-Jeghers syndrome is caused by mutations in a novel serine threoninekinase , 1998, Nature Genetics.

[5]  C. Amos,et al.  Fine mapping of a genetic locus for Peutz-Jeghers syndrome on chromosome 19p. , 1997, Cancer research.

[6]  S. H. Kim,et al.  Genetic alterations of p16INK4a and p53 genes in sporadic dysplastic nevus. , 1997, Biochemical and biophysical research communications.

[7]  Darryl Shibata,et al.  Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis , 1997, Nature Genetics.

[8]  N. Morton,et al.  A metric map of humans: 23,500 loci in 850 bands. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[9]  K. Kinzler,et al.  Lessons from Hereditary Colorectal Cancer , 1996, Cell.

[10]  T. C. Barnett,et al.  Single-tube protocol for the extraction of DNA or RNA from paraffin-embedded tissues using a starch-based adhesive. , 1996, BioTechniques.

[11]  Darryl Shibata,et al.  Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis , 1993, Nature.

[12]  S N Thibodeau,et al.  Microsatellite instability in cancer of the proximal colon. , 1993, Science.

[13]  J. Bufill,et al.  Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. , 1990, Annals of internal medicine.

[14]  B. Vogelstein,et al.  A genetic model for colorectal tumorigenesis , 1990, Cell.

[15]  A. Zauber,et al.  The National Polyp Study. Patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas. , 1990, Gastroenterology.

[16]  E. E. Gresch.  Genetic Alterations During Colorectal-Tumor Development , 1989 .

[17]  Y. Nakamura,et al.  Genetic alterations during colorectal-tumor development. , 1988, The New England journal of medicine.

[18]  A J Krush,et al.  Increased risk of cancer in the Peutz-Jeghers syndrome. , 1987, The New England journal of medicine.

[19]  V. McKusick,et al.  Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits; a syndrome of diagnostic significance. , 2010, The New England journal of medicine.