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Somatic Mutations in LKB1 Are Rare in Sporadic Colorectal and Testicular Tumors¹

Departments of Medical Genetics [E. A., S. R., A. L., A. H., L. A. A.] and Pathology [R. S.], Haartman Institute, University of Helsinki, FIN-00014 Helsinki, Finland; and Department of Genetics [R. A. L.], Institute of Cancer Research, and Departments of Pathology [A. E. S.] and Medical Oncology and Radiotherapy [S. D. F.], The Norwegian Radium Hospital, 0310 Oslo, Norway

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.

¹ This work was supported by the Academy of Finland, the Finnish Cancer Society, the Helsinki University Central Hospital, and the European Commission.

² To whom requests for reprints should be addressed, at Department of Medical Genetics, Haartman Institute, P.O. Box 21 (Haartmaninkatu 3), University of Helsinki, Fin-00014 Helsinki, Finland. Phone: 358-9-19126278; Fax: 358-9-19126677; E-mail: lauri.aaltonen@helsinki.fi.

Received 2/11/98. Accepted 3/31/98.

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