MUTYH-associated polyposis carcinomas
Tuesday 29 November 2011
Genetic instability is known to drive colorectal carcinogenesis. Generally, a distinction is made between two types of genetic instability: chromosomal instability (CIN) and microsatellite instability (MIN or MSI). Most CIN tumours are aneuploid, whereas MSI tumours are considered near-diploid.
However, for MUTYH-associated polyposis (MAP) the genetic instability involved in the carcinogenesis remains unclear, as near-diploid adenomas, aneuploid adenomas and near-diploid carcinomas have been reported.
One analysis of 26 MUTYH-associated polyposis carcinomas, using SNP arrays and flow sorting, showed that these tumours are often near-diploid (52%) and mainly contain chromosomal regions of copy-neutral loss of heterozygosity (LOH) (71%). This is in contrast to sporadic colon cancer, where physical loss is the main characteristic.
Copy-neutral LOH is an important mechanism in the tumorigenesis of MAP.
High frequency of copy-neutral LOH in MUTYH-associated polyposis carcinomas. Middeldorp A, van Puijenbroek M, Nielsen M, Corver WE, Jordanova ES, ter Haar N, Tops CM, Vasen HF, Lips EH, van Eijk R, Hes FJ, Oosting J, Wijnen J, van Wezel T, Morreau H. J Pathol. 2008 Sep;216(1):25-31. PMID: 18506705