title: Low-level microsatellite instability occurs in most colorectal cancers and is a nonrandomly distributed quantitative trait.
abstract: 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.
authors.affiliation: Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Halford
authors.forename: Peter
authors.initials: P
authors.lastname: Sasieni
authors.forename: Andrew
authors.initials: A
authors.lastname: Rowan
authors.forename: Harpreet
authors.initials: H
authors.lastname: Wasan
authors.forename: Walter
authors.initials: W
authors.lastname: Bodmer
authors.forename: Ian
authors.initials: I
authors.lastname: Talbot
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hawkins
authors.forename: Robyn
authors.initials: R
authors.lastname: Ward
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics*; D019655:Quantitative Trait, Heritable