SOMATIC MUTATIONS IN LKB1 ARE RARE IN SPORADIC COLORECTAL AND TESTICULAR-TUMORS

Germ-line mutations in a serine/threonine kinase gene, LKB1, were rece ntly shown to underlie Peutz-Jeghers syndrome (PJS), a hereditary diso rder that predisposes to benign and malignant tumors of multiple organ systems. Most mutations that have been described thus far dramaticall y change the predicted protein and are likely to be of an inactivating nature. This observation and a previous observation that the LKB1 loc us is often deleted in PJS polyps suggest that the gene may function a s a tumor suppressor. We examined whether somatic mutations in this ge ne 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 t umors. One testicular tumor displayed a heterozygous missense type var iant, in which glycine 163 was changed to aspartic acid. This change w as absent in the DNA of normal tissue. To better focus our efforts, we tested 75 additional colon carcinomas for loss of heterozygosity at 1 9p, where LKB1 is localized, Of 75 samples analyzed, 50 were informati ve with a closely linked marker, D19S886, and 13 (26%) of these displa yed loss of heterozygosity, The 13 tumors were scrutinized for LKB1 mu tations by genomic sequencing. This analysis revealed no changes. Toge ther, these findings suggest that somatic mutations of LKB1 are not fr equent in colorectal and testicular cancer.