Colorectal cancer, novel genes

Identification of novel genes predisposing to colorectal cancer.

KWF 2005-2009

Dr. Tom van Wezel, Dr. Juul Wijnen en Prof. Dr. Hans Morreau

Anneke Middeldorp, Shantie Jagmohan (technician)

Clinical genetics centers in the Netherlands receive many requests for counseling and advise about increased risk for colorectal cancer (CRC) in the family. In many cases the predisposing genes for these persons are not yet identified. We want to identify new predisposing genes with moderate and high penetrance in families with strong clustering of CRC employing different strategies of preselection.

We will use linkage analysis supported by high-resolution LOH mapping in MMR-mutation negative Amsterdam II criteria positive families with MSS tumors to preselect genomic regions where CRC predisposing genes reside.

Key publication ( s ) 

Jenkins MA, Baglietto L, Dite GS, Jolley DJ, Southey MC, Mead LJ, St John DJ, Macrae FA, Bishop DT, Venter DJ, Giles GG, Hopper JL. After hMSH2 an hMLH1- what next? Analysis of three-generational, population-based, early-onset colorectal cancer families. Int J Cancer 2002; 102: 166-171

de Jong AE, van Puijenbroek M, Hendriks Y, Tops C, Wijnen J, Ausems MG, Meijers-Heijboer H, Wagner A, van Os TA, Brocker-Vriends AH, Vasen HF, Morreau H. Microsatellite instability, immunohistochemistry, and additional PMS2 staining in suspected hereditary nonpolyposis colorectal cancer. Clin Cancer Res. 2004 Feb 1;10(3):972-80.