Molecular alterations associated with liver metastases development in colorectal cancer patients

• Published in: British journal of cancer 2011-07, Vol.105 (2), p.281-287
• Main Authors: Bruin, S C, He, Y, Mikolajewska-Hanclich, I, Liefers, G-J, Klijn, C, Vincent, A, Verwaal, V J, de Groot, K A, Morreau, H, van Velthuysen, M-L F, Tollenaar, R A E M, van ‘t Veer, L J
• Format: Article
• Language: English
• Subjects: 692/420/2489/144/68; 692/698/2741/288; 692/699/67/1504/1885; 692/699/67/322; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cancer therapies; Carcinoma - genetics; Carcinoma - pathology; Cell growth; Chromosome Aberrations; Chromosomes; Cohort Studies; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Disease Progression; DNA Mutational Analysis; Drug Resistance; Epidemiology; Female; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Genetics and Genomics; Genome-Wide Association Study; Humans; Liver; Liver Neoplasms - genetics; Liver Neoplasms - secondary; Male; Medical prognosis; Medical research; Medical sciences; Metastasis; Middle Aged; Molecular biology; Molecular Medicine; Mutation; Mutation - physiology; Oncology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surgery; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2011.184

Background: Understanding the molecular biology of colorectal cancer (CRC) provides opportunities for effective personalised patient management. We evaluated whether chromosomal aberrations, mutations in the PI(3)K signalling pathway and the CpG-island methylator phenotype (CIMP) in primary colorectal tumours can predict liver metastases. Methods: Formalin-fixed paraffin-embedded material from primary colorectal tumours of three different groups were investigated: patients with CRC without metastases (M0, n =39), patients who were treated with hyperthermal intraperitoneal chemotherapy for CRC metastases confined to the peritoneum (PM, n =46) and those who had isolated hepatic perfusion for CRC metastases confined to the liver (LM, n =48). Results: All samples were analysed for DNA copy number changes, PIK3CA , KRAS , BRAF mutations, CIMP and microsatellite instability. The primary CRCs of the LM group had significantly higher frequency of amplified chromosome 20q ( P =0.003), significantly fewer mutations in the PI(3)K signalling pathway ( P =0.003) and fewer CIMP high tumours ( P =0.05). There was a strong inverse correlation between 20q and the PI(3)K pathway mutations. Conclusion: The development of CRC liver metastases is associated with amplification of chromosome 20q and not driven by mutations in the PI(3)K signalling pathway.