Medline ® Abstract for Reference 112
of 'Molecular genetics of colorectal cancer'
Low-level microsatellite instability occurs in most colorectal cancers and is a nonrandomly distributed quantitative trait.
Halford S, Sasieni P, Rowan A, Wasan H, Bodmer W, Talbot I, Hawkins N, Ward R, Tomlinson I
Cancer Res. 2002;62(1):53.
About 10-15% of colorectal cancers show high-level microsatellite instability. The characteristics and very existence of low-level instability (MSI-L) are unclear, although some studies have found associations between MSI-L and molecular characteristics, notably more frequent K-ras mutations and a low level of allele loss near APC. We have attempted to define a MSI-L group of tumors by analyzing 107 sporadic colorectal carcinomas at 44 microsatellites. Ten (9.7%) MSI-H cancers were identified, but there was no evidence for a discrete MSI-L group. However, the 97 non-MSI-H cancers showed greater variation in the frequency of MSI than was expected by chance. Most cancers (68%) in the non-MSI-H group showed some MSI and could therefore be classed as nominally MSI-L. No association was found between MSI-L (or the level of MSI) and any clinicopathological or molecular variable, including K-ras mutation and loss of heterozygosity at APC. The causes of variation in level of the MSI in non-MSI-H colorectal cancers are unknown, but the differences are quantitative and probably reflect the evolutionary histories of the cancers rather than qualitatively different genetic pathways of tumorigenesis.
Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom.