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|Title:||Molecular alterations associated with liver metastases development in colorectal cancer patients|
de Groot, K.
van Velthuysen, M.
van't Veer, L.
|Citation:||British Journal of Cancer, 2011; 105(2):281-287|
|Publisher:||Cancer Research UK|
|S C Bruin, Y He, I Mikolajewska-Hanclich, G-J Liefers, C Klijn, A Vincent, V J Verwaal, K A de Groot, H Morreau, M-L F van Velthuysen, R A E M Tollenaar and L J van' t Veer|
|Abstract:||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.|
|Keywords:||Colorectal cancer; liver metastases; chromosome 20q; PI(3)K signalling pathway; PIK3CA; KRAS|
|Rights:||© 2011 Cancer Research UK All rights reserved. From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/|
|Appears in Collections:||Medicine publications|
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