CDX2 mutations do not account for juvenile polyposis or Peutz-Jeghers syndrome and occur infrequently in sporadic colorectal cancers

Peutz-Jeghers syndrome (PJS) and juvenile polyposis (JPS) are both characte rized by the presence of hamartomatous polyps and increased risk of maligna ncy in the gastrointestinal tract. Mutations of the LKB1 and SMAD4 genes ha ve been shown recently to cause a number of PJS and JPS cases respectively, but there remains considerable uncharacterized genetic heterogeneity in th ese syndromes. particularly JPS. The mouse homologue of CDX2 has been shown to give rise to a phenotype which includes hamartomatous-like polyps in th e colon and is therefore a good candidate for JPS and PJS cases which are n ot accounted for by the SMAD4 and LKB1 genes. By analogy with SMAD4. CDX2 i s also a candidate for somatic mutation in sporadic colorectal cancer. We h ave screened 37 JPS families/cases without known SMAD4 mutations, 10 Peutz- Jeghers cases without known LKB1 mutations and 49 sporadic colorectal cance rs for mutations in CDX2. Although polymorphic variants and rare variants o f unlikely significance were detected, no pathogenic CDX2 mutations were fo und in any case of JPS or PJS, or in any of the sporadic cancers. (C) 2001 Cancer Research Campaign.