Short Communications
Genetic Pathways of Colorectal Carcinogenesis Rarely Involve thePTEN and LKB1 Genes Outside the Inherited Hamartoma Syndromes

https://doi.org/10.1016/S0002-9440(10)65579-4Get rights and content

Germline mutations of the PTEN/MMAC1/TEP andLKB1 genes cause hamartomas to develop in the gastrointestinal tracts of patients with Cowden syndrome and Peutz-Jeghers syndrome, respectively. PTENmutations 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 andLKB1 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 inPTEN and LKB1. No variants predicted to alter protein function were detected in LKB1, but 1 of 72 cancers showed a somatic mutation inPTEN, together with allele loss. This cancer did not have a detectable APC mutation or allele loss atAPC. It remains possible that PTEN andLKB1 are inactivated in other sporadic colon cancers by means such as deletion or promoter methylation. LikeBRCA1 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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Supported in part by a grant from the Cancer Research Campaign. Z-JW is supported by the Chinese Government. IT is supported by the Jane Ashley Trust.

Zhen-Jung Wang and Fleur Taylor contributed equally to this work.

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