Fbxw7 hotspot mutations and human colon cancer: mechanistic insights from new mouse models

The recent explosion in cancer genomics provides an unprecedented view of the genetic changes present in solid tumours. The characterisation of colorectal cancer samples via DNA sequencing has confirmed the importance of established oncogene and tumour suppressor pathways (including the ‘mountains’ of Apc, Tp53 and Ras) but has also identified novel cancer genes that are mutated in a small percentage of patient samples (hills).1 2 Furthermore, these studies give a new appreciation of the spectrum of gene mutations present in cancers, especially in candidate tumour suppressor genes (TSGs). While classic genetics teaches that two hits are required to inactivate TSGs, sequencing studies show that heterozygous mutations are also quite frequent. Some of these are loss of function alleles, while others are recurrent missense mutations known as ‘hotspots’. Now, researchers are charged with the task of understanding how these genetic changes contribute to cancer development,...

Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Grim, J. E. Tags: Commentary Source Type: research