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

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.

journal_name

BMC Cancer

journal_title

BMC cancer

authors

Bruin SC,Klijn C,Liefers GJ,Braaf LM,Joosse SA,van Beers EH,Verwaal VJ,Morreau H,Wessels LF,van Velthuysen ML,Tollenaar RA,Van't Veer LJ

doi

10.1186/1471-2407-10-662

subject

Has Abstract

pub_date

2010-12-02 00:00:00

pages

662

issn

1471-2407

pii

1471-2407-10-662

journal_volume

10

pub_type

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