Impact of somatic mutations on patterns of metastasis in colorectal cancer
Open Access
- 1 December 2015
- journal article
- review article
- Vol. 6 (6), 645-649
- https://doi.org/10.3978/j.issn.2078-6891.2015.045
Abstract
Somatic mutation status in metastatic colorectal cancer (mCRC) is becoming increasingly clinically relevant as it may be correlated not only with response to biologic therapies, but also with site-specific pattern of metastatic spread and outcome. In this review, we describe our current understanding of associations between mutational activation of the KRAS, BRAF, PIK3CA, and NRAS oncogenes and clinical outcomes and metastatic patterns of mCRC. The presence of a KRAS mutation is associated with a distinct pattern of metastatic spread with decreased liver metastases and increased lung, brain, and bone metastases. In patients who undergo resection of colorectal liver metastases (CLM) with curative intent, KRAS mutation is associated increased risk of recurrence, worse survival, and increased recurrence outside of the liver, particularly in the lung, but also in the brain and bone. BRAF mutation, a poor prognostic factor in mCRC, is associated with decreased liver-limited metastasis and increased peritoneal and distant lymph node metastases. PIK3CA mutation does not clearly affect outcomes in the metastatic setting, but is associated with concurrent KRAS mutations, and has been associated with an increased incidence of lung and brain metastases, metastatic sites preferentially involved in KRAS mutant mCRC. NRAS mutation may confer worse survival and early studies suggest NRAS mutation may promote tumorigenesis in the setting of colorectal inflammation. As metastasectomy with curative intent is increasingly considered in patients with mCRC, understanding patterns of metastasis associated with tumor mutations may help focus medical treatment, surgical management, and surveillance in patients with mCRC.Keywords
This publication has 29 references indexed in Scilit:
- Axillary Lymph Node Involvement, a Unique Pattern of Metastasis inBRAF-Mutant Colorectal CancerJAMA Oncology, 2015
- Colon cancer cells colonize the lung from established liver metastases through p38 MAPK signalling and PTHLHNature, 2014
- BRAF-activated long non-coding RNA contributes to colorectal cancer migration by inducing epithelial-mesenchymal transitionOncology Letters, 2014
- RAS Mutation Status Predicts Survival and Patterns of Recurrence in Patients Undergoing Hepatectomy for Colorectal Liver MetastasesAnnals of Surgery, 2013
- Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastasesCancer, 2013
- Comprehensive molecular characterization of human colon and rectal cancerNature, 2012
- BRAF-mutated, Microsatellite-stable Adenocarcinoma of the Proximal ColonThe American Journal of Surgical Pathology, 2012
- BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancerBritish Journal of Cancer, 2011
- Genomic and Biological Characterization of Exon 4 KRAS Mutations in Human CancerCancer Research, 2010
- Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal CancerJournal of Clinical Oncology, 2008