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Open Access Research article

Specific genomic aberrations in primary colorectal cancer are associated with liver metastases

Sjoerd C Bruin1, Christiaan Klijn23, Gerrit-Jan Liefers4, Linde M Braaf4, Simon A Joosse56, Eric H van Beers5, Victor J Verwaal7, Hans Morreau8, Lodewyk F Wessels23, Marie-Louise F van Velthuysen9, Rob AEM Tollenaar4 and Laura J van't Veer10*

Author Affiliations

1 Division of Experimental Therapy, Department of Surgery, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands

2 Department of Molecular Biology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands

3 Delft University of Technology, Delft Bioinformatics Lab., PO Box 5031. 2600 GA, Delft, The Netherlands

4 Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands

5 Division of Experimental Therapy, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands

6 Institute of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany

7 Department of Surgery, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands

8 Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

9 Department of Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands

10 Division of Experimental Therapy, Department of Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands

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BMC Cancer 2010, 10:662  doi:10.1186/1471-2407-10-662

Published: 2 December 2010

Abstract

Background

Accurate staging of colorectal cancer (CRC) with clinicopathological parameters is important for predicting prognosis and guiding treatment but provides no information about organ site of metastases. Patterns of genomic aberrations in primary colorectal tumors may reveal a chromosomal signature for organ specific metastases.

Methods

Array Comparative Genomic Hybridization (aCGH) was employed to asses DNA copy number changes in primary colorectal tumors of three distinctive patient groups. This included formalin-fixed, paraffin-embedded tissue of patients who developed liver metastases (LM; n = 36), metastases (PM; n = 37) and a group that remained metastases-free (M0; n = 25).

A novel statistical method for identifying recurrent copy number changes, KC-SMART, was used to find specific locations of genomic aberrations specific for various groups. We created a classifier for organ specific metastases based on the aCGH data using Prediction Analysis for Microarrays (PAM).

Results

Specifically in the tumors of primary CRC patients who subsequently developed liver metastasis, KC-SMART analysis identified genomic aberrations on chromosome 20q. LM-PAM, a shrunken centroids classifier for liver metastases occurrence, was able to distinguish the LM group from the other groups (M0&PM) with 80% accuracy (78% sensitivity and 86% specificity). The classification is predominantly based on chromosome 20q aberrations.

Conclusion

Liver specific CRC metastases may be predicted with a high accuracy based on specific genomic aberrations in the primary CRC tumor. The ability to predict the site of metastases is important for improvement of personalized patient management.