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STK11 Mutations in Peutz-Jeghers Syndrome and Sporadic Colon Cancer¹

Dipartimento di Medicina Interna e del Lavoro, Sezione di Genetica Medica [N. R., C. S., F. S., G. G.], Istituto di Anatomia Patologica Policlinico [P. B.], and Cattedra di Gastroenterologia Policlinico [M. I.], Bari 70124; IRCCS "De Bellis" Genetica Medica, Castellana (Ba) 70013 [M. G., R. G.]; D.I.M.I. [C. M., M. M.] and Centro Biotecnologie Avanzate [S. P.], Università di Genova, Genova 16132; Servizio di Gastroenterologia-Endoscopia Digestiva, Ospedale San Giovanni, Torino 10123 [F. P. R.]; Istituto Tumori Milano, Milan 20133 [L. B.]; Divisione di Chirurgia Generale e Trapianti d'Organo, Università Federico II, Nuovo Policlinico, Naples 80131 [N. C.]; and Dipartimento di Pediatria, Servizio di Genetica Medica, Padova 35128 [R. T.], Italy

A potential tumor suppressor gene, STK11, encoding a serine threonine kinase, has recently been identified on chromosome 19p13. Germ-line mutations of this gene have been found in patients with Peutz-Jeghers syndrome (PJS). To further investigate the relevance of STK11 mutations in PJS, we analyzed its coding sequence in nine patients and identified two deletions and three missense mutations. Because intestinal carcinomas have been observed to develop in association with PJS, we analyzed tumors from 71 patients for allelic deletions (loss of heterozygosity) and STK11 gene mutations, to elucidate the etiological role of STK11 gene in sporadic colorectal cancer. Loss of heterozygosity, evaluated using the microsatellite D19S886, was observed in 10 of 52 informative cases. No somatic mutations were detected except for a missense alteration in one tumor. Our data indicate the heterogeneity of PJS and the infrequent involvement of the STK11 gene in colorectal cancer.

¹ Supported by grants from the Associazione Italiana Ricerca sul Cancro, Ministero dell'Università e Ricerca Scientifica e Tecnologica (40%), and Byk Gulden.

² To whom requests for reprints should be addressed, at Dipartimento di Medicina Interna e del Lavoro, Sezione di Genetica Medica, Policlinico, Piazza Giulio Cesare 70124 Bari, Italy. Phone: 39-805478270; Fax: 39-805478269; E-mail: guanti@medgene.uniba.it.

Received 6/29/98. Accepted 9/17/98.

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