title: Somatic mutations in LKB1 are rare in sporadic colorectal and testicular tumors.
abstract: Germ-line mutations in a serine/threonine kinase gene, LKB1, were recently shown to underlie Peutz-Jeghers syndrome (PJS), a hereditary disorder that predisposes to benign and malignant tumors of multiple organ systems. Most mutations that have been described thus far dramatically change the predicted protein and are likely to be of an inactivating nature. This observation and a previous observation that the LKB1 locus is often deleted in PJS polyps suggest that the gene may function as a tumor suppressor. We examined whether somatic mutations in this gene are present in sporadic carcinomas of the colon and testis, tumors that are characteristic of PJS. First, 20 randomly selected colorectal and 28 testicular tumors were analyzed by single-strand conformation polymorphism analysis. No mutations in LKB1 were found in colorectal tumors. One testicular tumor displayed a heterozygous missense type variant, in which glycine 163 was changed to aspartic acid. This change was absent in the DNA of normal tissue. To better focus our efforts, we tested 75 additional colon carcinomas for loss of heterozygosity at 19p, where LKB1 is localized. Of 75 samples analyzed, 50 were informative with a closely linked marker, D19S886, and 13 (26%) of these displayed loss of heterozygosity. The 13 tumors were scrutinized for LKB1 mutations by genomic sequencing. This analysis revealed no changes. Together, these findings suggest that somatic mutations of LKB1 are not frequent in colorectal and testicular cancer.
authors.affiliation: Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Avizienyte
authors.forename: S
authors.initials: S
authors.lastname: Roth
authors.forename: A
authors.initials: A
authors.lastname: Loukola
authors.forename: A
authors.initials: A
authors.lastname: Hemminki
authors.forename: R A
authors.initials: RA
authors.lastname: Lothe
authors.forename: A E
authors.initials: AE
authors.lastname: Stenwig
authors.forename: S D
authors.initials: SD
authors.lastname: Fosså
authors.forename: R
authors.initials: R
authors.lastname: Salovaara
authors.forename: L A
authors.initials: LA
authors.lastname: Aaltonen
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000230:Adenocarcinoma / Q000235:genetics*; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis*; D005091:Exons / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D016415:Sequence Alignment; D013736:Testicular Neoplasms / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases