Editor—PTEN, a tumour suppressor gene located in chromosome 10q23, is homologous to tyrosine and dual specificity phosphatases with a high degree of substrate specificity. This enzymatic activity is necessary forPTEN/MMAC1 tumour suppressor function.1-4 Mutations of this gene have been identified in many glioma, glioblastoma, prostate, kidney, and breast carcinoma cell lines and in primary tumours including gliomas, and breast, thyroid, and kidney carcinomas.1 2 5 Germline mutations of the PTEN gene underlie Cowden disease, an autosomal dominant disorder associated with an increased risk of breast and thyroid cancer and possibly endometrial malignancy. Benign tumours of the intestine (hamartomas) and skin (such as trichilemmomas) also occur.6 7

LKB1, a candidate tumour suppressor gene, encodes a serine/threonine kinase which is highly homologous (84%) to Xenopus serine/threonine kinase XEEK1.8 Germline mutations in LKB1 have been associated with Peutz-Jeghers syndrome (PJS).9 10 Jenneet al 10 report that their success in identifying the gene by analysing only two candidate sequences was based on strong linkage disequilibrium. This is surprising, as while linkage disequilibrium is a powerful tool in disease gene identification, no linkage disequilibrium has been reported in PJS and the patients typically display different mutations.9 10 PJS is characterised by hamartomatous intestinal polyposis, mucocutaneous …