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Updated: Aug 16, 2026
In vitro Organoid Culture of Primary Mouse Colon Tumors
Published on: May 17, 2013
DCC and SMAD4 alterations in human colorectal and pancreatic tumor dissemination
G Tarafa1, A Villanueva, L Farré
1Laboratori D'Investigació Gastrointestinal, Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Abstract:
Chromosome 18q is lost a high proportion of colorectal and pancreatic cancers. Three candidate tumor suppressor genes, DCC, Smad4 and Smad2 have been identified in this chromosome region. DCC and Smad4 aberrations have been previously identified in pancreatic and colorectal tumors. The aim of this study was to compare the presence of concurrent genetic aberrations in DCC and neighboring Smad4 and Smad2 genes during colorectal and pancreatic distal dissemination. We have used a panel of orthotopically implanted colorectal and pancreatic xenografts and corresponding metastases. We have shown that while LOH at DCC locus occurred at a similar frequency in both tumors, diminished DCC protein expression was exclusively present in colorectal tumors harboring intragenic DCC LOH. In contrast, in pancreatic xenografts loss of DCC protein and mRNA expression was restricted to metastases. Smad4 gene aberrations were detected at a similar frequency in both tumors and were selected for during distal dissemination. Acquisition of alterations in both genes occurred independently. Our results suggest that both DCC and Smad4 contribute to pancreatic and colorectal distal dissemination. However, the role of DCC may differ between both tumor types.
Insights
Genetic aberrations in DCC and Smad4 genes on chromosome 18q contribute to tumor spread in colorectal and pancreatic cancers. The specific role of DCC differs between these cancer types.
Area of Science:
- Oncology
- Cancer Genetics
- Molecular Biology
Background:
- Chromosome 18q deletions are common in colorectal and pancreatic cancers.
- Candidate tumor suppressor genes DCC, Smad4, and Smad2 are located on chromosome 18q.
- Previous studies identified DCC and Smad4 aberrations in these tumors.
Purpose of the Study:
- To compare concurrent genetic aberrations in DCC, Smad4, and Smad2 during colorectal and pancreatic cancer metastasis.
- To investigate the role of these genes in tumor dissemination.
Main Methods:
- Utilized orthotopically implanted colorectal and pancreatic xenografts and their metastases.
- Analyzed loss of heterozygosity (LOH) at the DCC locus.
- Assessed DCC protein and mRNA expression.
- Examined Smad4 gene aberrations.
Main Results:
- DCC LOH occurred similarly in both tumor types, but diminished DCC protein expression was linked to intragenic DCC LOH in colorectal tumors.
- In pancreatic xenografts, DCC protein and mRNA loss was specific to metastases.
- Smad4 gene aberrations were frequent in both tumor types and selected for during metastasis.
- Alterations in DCC and Smad4 occurred independently.
Conclusions:
- Both DCC and Smad4 play roles in the distal dissemination of pancreatic and colorectal cancers.
- The specific contribution of DCC to tumor spread may vary between colorectal and pancreatic cancers.
