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

• Published in: BMC cancer Vol. 10; no. 1; p. 662
• Main Authors: Bruin, Sjoerd C, Klijn, Christiaan, Liefers, Gerrit-Jan, Braaf, Linde M, Joosse, Simon A, van Beers, Eric H, Verwaal, Victor J, Morreau, Hans, Wessels, Lodewyk F, van Velthuysen, Marie-Louise F, Tollenaar, Rob A E M, Van't Veer, Laura J
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.12.2010; BioMed Central; BMC
• Subjects: Adult; Aged; Breast cancer; Cancer; Cancer therapies; Care and treatment; Chemotherapy; Chi-Square Distribution; Chromosome Aberrations; Chromosomes; Chromosomes, Human, Pair 20; Clinical medicine; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Colorectal Neoplasms - therapy; Comparative Genomic Hybridization; Data collection; Databases, Genetic; Development and progression; Female; Fixatives; Formaldehyde; Gene Dosage; Gene Expression Profiling - methods; Genetic aspects; Genetic Predisposition to Disease; Health aspects; Hospitals; Humans; Liver diseases; Liver Neoplasms - genetics; Liver Neoplasms - mortality; Liver Neoplasms - secondary; Liver Neoplasms - therapy; Logistic Models; Male; Middle Aged; Neoplasm Staging; Netherlands; Oligonucleotide Array Sequence Analysis; Paraffin Embedding; Pathology; Phenotype; Physiological aspects; Predictive Value of Tests; Risk factors; Statistical analysis; Survival Analysis; Time Factors; Tissue Fixation - methods; Treatment Outcome; Tumors; Netherlands
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-10-662

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. 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). 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. 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.