Background and aims: Loss of DNA sequences from chromosome 18q21 is a major genetic change in colorectal tumorigenesis. Multiple genes have been identified in this area. One of these, DPC4 (deleted in pancreatic cancer 4, also known as SMAD4), is mutated in a minor subset of colorectal carcinomas as well as in germlines of humans predisposed to colon tumours.
Patients and methods: The involvement of SMAD4 in sporadic colorectal neoplasia was evaluated by immunohistochemistry in 53 unselected cases and 27 cases displaying microsatellite instability.
Results: SMAD4 expression was absent in 20 of 53 (38%) unselected colorectal carcinomas, and reduced in another 15 (28%) cases. However, 26 of 27 cancers displaying microsatellite instability and TGF-βIIR mutations were positive for SMAD4 immunostaining.
Conclusions: Loss of SMAD4 expression may play a more prominent role in colon cancer than anticipated based on genetic evidence, but not in mutator phenotype tumours.
- colorectal carcinoma
- MSI, microsatellite instability
- LOH, loss of heterozygosity
- RT-PCR, reverse transcription-polymerase chain reaction
- TGF-βIIR, transforming growth factor β type II receptor
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Reproduced in full with permission from Gut 2002;51;56–59
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