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(American Journal of Pathology. 1998;153:363-366.)
© 1998 American Society for Investigative Pathology

Short Communications

Genetic Pathways of Colorectal Carcinogenesis Rarely Involve the PTEN and LKB1 Genes Outside the Inherited Hamartoma Syndromes

Zhen-Jung Wang* , Fleur Taylor* , Michael Churchman* , Gail Norbury and Ian Tomlinson*§

From the Tumour Genetics Group,* Nuffield Department of Clinical Medicine, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom; Department of Surgery, First Teaching Hospital, Beijing, China; NHS Molecular Genetics Laboratory, Churchill Hospital, Oxford, United Kingdom; and Molecular and Population Genetics Laboratory,§ Imperial Cancer Research Fund, London, United Kingdom

Germline mutations of the PTEN/MMAC1/TEP and LKB1 genes cause hamartomas to develop in the gastrointestinal tracts of patients with Cowden syndrome and Peutz-Jeghers syndrome, respectively. PTEN mutations may also be responsible for some cases of juvenile polyposis. Histologically, hamartomas appear benign, but there is good evidence that in these syndromes, the hamartomas can progress to colorectal carcinoma. It remains unknown whether or not cancers that develop from hamartomas acquire a spectrum of mutations similar to those in sporadic colon cancers. PTEN and LKB1 are candidate genes for mutations in sporadic colon cancers, either as initiating events in tumorigenesis or providing a selective advantage during tumor growth. Using single-strand conformational polymorphism analysis, we have screened a set of sporadic colon cancers for somatic mutations in PTEN and LKB1. No variants predicted to alter protein function were detected in LKB1, but 1 of 72 cancers showed a somatic mutation in PTEN, together with allele loss. This cancer did not have a detectable APC mutation or allele loss at APC. It remains possible that PTEN and LKB1 are inactivated in other sporadic colon cancers by means such as deletion or promoter methylation. Like BRCA1 and BRCA2, however, it appears that PTEN and LKB1 mutations can cause cancers when present in the germline, but occur rarely in the soma.

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