Microsatellite instability in the insulin-like growth factor II receptor gene in gastrointestinal tumours

Microsatellites are oligonucleotide repeat sequences present throughout the human genome. The appearance of mutations within these regions, consisting of additions or deletions of repeat units, are known as the replication/repair error-positive (RER+) phenotype or microsatellite instability (MI). MI has been demonstrated in multiple primary human tumour types. However, most MI has thus far been described in noncoding DNA, within introns or intergenic regions of the genome. Recently, the first target of MI within a coding region was identified in the transforming growth factor-beta type II receptor (TGF beta 1RII) gene in colon cancer cells. Deletions or insertions of one or two bases were reported in a poly-deoxyadenine tract within the upstream portion of the cDNA. These mutations generated nonsense codons downstream and were predicted to yield truncated, non-functional proteins. Microsatellite mutation within the coding region of TGF beta 1RII is present in RER+ primary gastric and ulcerative colitis-associated cancers, in addition to sporadic colorectal cancers. Thus, there is strong evidence supporting the importance of TGF beta 1 and its receptors in gastrointestinal tumorigenesis.