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

Abstract

BackgroundAccurate 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.MethodsArray 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).ResultsSpecifically 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.ConclusionLiver 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.

Molecular alterations associated with liver metastases development in colorectal cancer patients

“…Furthermore, in our recent work we showed that an amplification of chromosome 20q is strongly related with the development of liver metastases (Bruin et al , 2010). …”

Cancers of the Colon and Rectum: Identical or Fraternal Twins?

“…For rectal cancer in particular, gene expression profiling has been used to identify a gene signature of local recurrence after chemoradiation therapy, but, for reasons described previously, there is no colon cancer comparison in this study (12). In addition, gene expression profiling has led to the identification of biomarkers related to colorectal cancer staging, metastatic behavior, and clinical response, but these studies typically have not evaluated colon cancer and rectal cancer separately (13)(14)(15). For studies in which data are available for anatomic location, there are significant differences in mRNA and miRNA expression between colon cancers and rectal cancers (15,16).…”

Reduced rate of copy number aberrations in mucinous colorectal carcinoma

“…[ 33 ] One study that analyzed CNAs between patients with different metastatic patterns showed that gain of the 20q chromosomal arm was associated with liver-specific metastases, suggesting a role in the process of liver metastasis in CRC. [ 34 ] Patients who did not develop metastatic disease and patients with peritoneal metastases showed a gain of 20q less frequently. [ 34 , 35 ] These findings fit very well with the aberrant metastatic pattern that has been observed in MC patients.…”