Frequent loss of SMAD4/DPC4 protein in colorectal cancers
- R Salovaara1,
- S Roth2,
- A Loukola2,
- V Launonen2,
- P Sistonen3,
- E Avizienyte2,
- P Kristo2,
- H Järvinen4,
- S Souchelnytskyi5,
- M Sarlomo-Rikala6,
- L A Aaltonen7
- 1Department of Medical Genetics and Department of Pathology, Haartman Institute, PO Box 63, FIN-00014 University of Helsinki, Finland
- 2Department of Medical Genetics, Haartman Institute, PO Box 63, FIN-00014 University of Helsinki, Finland
- 3Finnish Red Cross Blood Transfusion Service, Kivihaantie 7, FIN-00310 Helsinki, Finland
- 4Second Department of Surgery, Helsinki University Central Hospital, PO Box 340, FIN-00029 Helsinki, Finland
- 5Ludwig Institute for Cancer Research, PO Box 595, S-751 24 Uppsala, Sweden
- 6Department of Pathology, Haartman Institute, PO Box 63, FIN-00014 University of Helsinki, Finland
- 7Department of Medical Genetics, Haartman Institute, PO Box 63, FIN-00014 University of Helsinki, Finland, and Department of Oncology, Helsinki University Central Hospital, PO Box 180, FIN-00029 Helsinki, Finland
- Correspondence to: Dr L A Aaltonen, Department of Medical Genetics, Haartman Institute, PO Box 63, FIN-00014 University of Helsinki, Finland; lauri.aaltonen{at}helsinki.fi.
- Accepted 17 September 2001
Abstract
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.
- MSI, microsatellite instability
- LOH, loss of heterozygosity
- RT-PCR, reverse transcription-polymerase chain reaction
- TGF-βIIR, transforming growth factor β type II receptor
Footnotes
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Reproduced in full with permission from Gut 2002;51;56–59
