Heterozygous germline PTEN mutations cause Cowden syndrome. The risk of colorectal cancer in Cowden patients, however, remains a matter of debate. We describe two patients presenting with colorectal cancer at a young age (28 and 39 years) and dysmorphisms fitting the Cowden spectrum. Heterozygous germline mutations in PTEN were found in both patients. Moreover, analysis of the resected colorectal cancer specimens revealed loss of heterozygosity at the PTEN locus with retention of the mutated alleles, and greatly reduced or absent PTEN expression. Histologically and molecularly, the tumours showed resemblance with sporadic colorectal cancers, although they had prominent fibrotic stroma. Our data indicate that PTEN loss was involved in carcinogenesis in the two patients, supporting that colorectal cancer is part of the Cowden syndrome-spectrum. This is in line with data on sporadic colorectal cancer, mice studies and emerging epidemiological data on Cowden syndrome. Although the exact role of germline PTEN mutations in the carcinogenesis of colorectal cancer remains unclear, we think that Cowden syndrome should be in the differential diagnosis of colorectal cancer certainly in view of the possible prognostic and therapeutic consequences. Prospective follow-up and surveillance of PTEN mutation carriers from the age of 25 to 30 years in a study setting should clarify this issue.

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doi.org/10.1111/j.1399-0004.2011.01639.x, hdl.handle.net/1765/32368
Clinical Genetics: an international journal of genetics and molecular medicine
Erasmus MC: University Medical Center Rotterdam

Kersseboom, R, Dubbink, H.J, Corver, W.E, van Tilburg, A.J.P, Poley, J.-W, van Leerdam, M.E, … Wagner, A. (2012). PTEN in colorectal cancer: A report on two Cowden syndrome patients. Clinical Genetics: an international journal of genetics and molecular medicine, 81(6), 555–562. doi:10.1111/j.1399-0004.2011.01639.x