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DCC and SMAD4 alterations in human colorectal and pancreatic tumor dissemination

Oncogene volume 19, pages 546–555 (2000)Cite this article

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.

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Abbreviations

IHC:

immunohistochemistry

LOH:

loss of heterozygosity

SSCP:

single strand conformation polymorphism

STS:

sequence-tagged site

Mab:

monoclonal antibody

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Acknowledgements

This work was supported in part by grants from Comisión Interministerial de Ciencia y Tecnología (SAF95-281, SAF96-187-C02-01, SAF97-214 and SAF98-42); Marató TV3 (11–95) and (26–95); Laboratorios Dr Esteve SA and Fundació Catalana de Gastroenterologia. We thank the Pathology Department at the Hospital of Sant Pau and the Servei Cientifico-Tècnics de la Universitat de Barcelona for technical support.

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Authors and Affiliations

  1. Laboratori d'Investigació Gastrointestinal, Institut de Recerca, Hospital de la Santa Creu i Sant Pau,

    G Tarafa, A Villanueva, L Farré, G Reyes & G Capellá

  2. Av. Ant. M. Claret 167, Barcelona, 08025, Spain

    G Tarafa, A Villanueva, L Farré, G Reyes & G Capellá

  3. S. Cirurgia Vascular, Hospital de la Santa Creu i Sant Pau, Av. Ant. M. Claret 167, Barcelona, 08025, Spain

    J Rodríguez

  4. Servei de Patologia, Consorci Hospitalari Parc Taulí, Parc Taulí s/n, Sabadell, 08023, Spain

    E Musulén

  5. Serveis Cientifico-Tècnics de la Universitat de Barcelona, Lluís Solé i Sabarís 1-3, Barcelona, 08028, Spain

    R Seminago

  6. Departament de Biologia Cellular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Casanova 143, Barcelona, 08036, Spain

    E Olmedo, AB Paules & O Bachs

  7. Departament de Càncer i Metàstasi, Institut de Recerca Oncològica,

    MA Peinado

  8. Av. Gran Via s/n, km 2,7 08907 L'Hospitalet, Barcelona, Spain

    MA Peinado

  9. Institut Català d'Oncologia. Av. Gran Via s/n, km 2,7 08907 L'Hospitalet, Barcelona, Spain

    G Capellá

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  1. G Tarafa
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Tarafa, G., Villanueva, A., Farré, L. et al. DCC and SMAD4 alterations in human colorectal and pancreatic tumor dissemination. Oncogene 19, 546–555 (2000). https://doi.org/10.1038/sj.onc.1203353

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  • DOI: https://doi.org/10.1038/sj.onc.1203353

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