PTEN in colorectal cancer: a report on two Cowden syndrome patients
Article first published online: 9 MAR 2011
© 2011 John Wiley & Sons A/S
Volume 81, Issue 6, pages 555–562, June 2012
How to Cite
Kersseboom, R., Dubbink, H., Corver, W., van Tilburg, A., Poley, J., van Leerdam, M., Atmodimedjo, P., van de Laar, I., Collée, J., Dinjens, W., Morreau, H. and Wagner, A. (2012), PTEN in colorectal cancer: a report on two Cowden syndrome patients. Clinical Genetics, 81: 555–562. doi: 10.1111/j.1399-0004.2011.01639.x
- Issue published online: 4 MAY 2012
- Article first published online: 9 MAR 2011
- Accepted manuscript online: 3 FEB 2011 11:39AM EST
- Received 26 October 2010, revised and accepted for publication 31 January 2011
- colorectal cancer risk;
- Cowden syndrome;
- PTEN hamartoma tumour syndrome
Kersseboom R, Dubbink HJ, Corver WE, van Tilburg AJP, Poley JW, van Leerdam ME, Atmodimedjo PN, van de Laar IMBH, Collée JM, Dinjens WNM, Morreau H, Wagner A. PTEN in colorectal cancer; a report on two Cowden syndrome patients.
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.