Frequent loss of SMAD4/DPC4 protein in colorectal cancers.
OBJECTIVE
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.


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-betaIIR 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.
Salovaara
R
R
Department of Medical Genetics, Haartman Institute, PO Box 63, FIN-00014 University of Helsinki, Finland.
Roth
S
S
Loukola
A
A
Launonen
V
V
Sistonen
P
P
Avizienyte
E
E
Kristo
P
P
Järvinen
H
H
Souchelnytskyi
S
S
Sarlomo-Rikala
M
M
Aaltonen
L A
LA
D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D017353:Gene Deletion; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D051901:Smad4 Protein; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics*
D004268:DNA-Binding Proteins; D005819:Genetic Markers; D018125:Receptors, Transforming Growth Factor beta; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II