Allele loss and mutation screen at the Peutz-Jeghers (LKB1) locus (19p13.3) in sporadic ovarian tumours

Germline mutations in the LKB1 (STK11) gene (chromosome sub-band 19p13.3) c ause characteristic hamartomas and pigmentation to develop in patients with Peutz-Jeghers syndrome. Peutz-Jeghers syndrome carries an overall risk of cancer that may be up to 20 times that of the general population and Peutz- Jeghers patients are at increased risk of benign and malignant ovarian tumo urs, particularly granulosa cell tumours. Loss of heterozygosity (allele lo ss, LOH) has been reported in about 50% of ovarian cancers on 19p13.3, LKB1 is therefore a candidate tumour suppressor gene for sporadic ovarian tumou rs. We found allele loss at the marker D19S886(19p13.3) in 12 of 49 (24%) s poradic ovarian adenocarcinomas. Using SSCP analysis, we screened ten ovari an cancers with LOH, 35 other ovarian cancers and 12 granulosa cell tumours of the ovary for somatic mutations in LKB1. No variants were detected in a ny of the adenocarcinomas. Two mutations were detected in one of the granul osa cell tumours: a mis-sense mutation affecting the putative 'start' codon (ATG --> ACG, M1T); and a silent change in exon 7 (CTT --> CTA, leucine). Like BRCA1 and BRCA2, therefore, it appears that LKB1 mutations can cause o varian tumours when present in the germline, but occur rarely in the soma. The allele loss on 19p13.3 in ovarian cancers almost certainly targets a di fferent gene from LKB1.