RT Journal Article SR Electronic T1 STRAD in Peutz-Jeghers syndrome and sporadic cancers JF Journal of Clinical Pathology JO J Clin Pathol FD BMJ Publishing Group Ltd and Association of Clinical Pathologists SP 1091 OP 1095 DO 10.1136/jcp.2005.026013 VO 58 IS 10 A1 W W J de Leng A1 J J Keller A1 S Luiten A1 A R Musler A1 M Jansen A1 A F Baas A1 F W M de Rooij A1 J J P Gille A1 F H Menko A1 G J A Offerhaus A1 M A J Weterman YR 2005 UL http://jcp.bmj.com/content/58/10/1091.abstract AB Background/Aims:LKB1 is a tumour suppressor gene that is associated with Peutz-Jeghers syndrome (PJS), a rare autosomal dominant cancer predisposition syndrome. However, germline mutations in the LKB1 gene are found in only about 60% of patients with PJS, suggesting the existence of a second PJS gene. The STRAD gene, encoding an LKB1 interacting protein that activates LKB1, which subsequently leads to polarisation of cells, is an interesting candidate for a second PJS gene and a potential tumour suppressor gene in sporadic carcinomas. Methods: The involvement of STRAD in 42 PJS associated tumours (sporadic lung, colon, gastric, and ovarian adenocarcinomas) was studied using loss of heterozygosity (LOH) analysis of eight microsatellite markers on chromosome 17, including TP53, BRCA1, and STRAD markers. Results: Loss of the marker near the STRAD locus was seen in 13 of 29 informative cases, including all gastric adenocarcinomas. Specific LOH of the STRAD marker was found in four of 29 informative cases. For these patients all exons and exon–intron boundaries of the STRAD gene were sequenced, but no somatic mutations were identified. Furthermore, no germline STRAD mutations were found in 10 patients with PJS and family members without LKB1 germline mutation. Conclusions: Despite the frequent occurrence of LOH in the STRAD region, these results indicate that inactivation of the STRAD gene is not essential in the sporadic adenocarcinomas studied, although it is possible that STRAD may be inactivated in different ways. In addition, no evidence was found for the hypothesis that STRAD is a second PJS susceptibility gene.