The molecular heterogeneity of sporadic colorectal cancer with different tumor sites in Chinese patients
Open Access
- 14 March 2017
- journal article
- Published by Impact Journals, LLC in Oncotarget
- Vol. 8 (30), 49076-49083
- https://doi.org/10.18632/oncotarget.16176
Abstract
// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Junjie Peng1, 2, *, Dan Huang2, 3, *, Graeme Poston4, Xiaoji Ma1, 2, Renjie Wang1, 2, Weiqi Sheng2, 3, Xiaoyan Zhou2, 3, Xiaoli Zhu2, 3 and Sanjun Cai1, 2 1Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China 3Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China 4Department of Surgery, Aintree University Hospital, Liverpool L9 7AL, UK *These authors have contributed equally to this work Correspondence to: Junjie Peng, email: pengjj@shca.org.cn Keywords: colorectal cancer, RAS, BRAF, mutation, heterogeneity Received: August 31, 2016 Accepted: November 22, 2016 Published: March 14, 2017 ABSTRACT Purpose: To assess the biological variability of clinical meaningful molecular markers and their clinical correlations in Chinese patients with colorectal cancer (CRC). Materials and methods: In this prospective observational study, frequencies and clinico-pathological features of RAS and BRAFV600E mutations, deficiency of DNA mismatch repair (dMMR) were evaluated in patients with colorectal cancer staged I-IV. The molecular heterogeneity between right-sided and left-sided colorectal cancers was studied in our series by classifying patients with different mutations and dMMR status. Results: Among 400 evaluable patients, mutations in KRAS exon 2, exon 3 or 4, NRAS and BRAFV600E were detected in 36%, 7.5%, 3.5% and 2.5%, respectively. RAS mutations were significantly higher in metastatic CRCs (56.4% vs. 43.1%, p=0.015) and right-sided CRCs (62.5% vs 41.7%, p=0.003). In 212 RAS wild-type patients, V600E mutation was higher in older patients (9.5% vs. 2.2%, p=0.017), women (9.2% vs. 2.2%, p=0.021) and right-sided CRCs (10.5% vs. 3.4%, p=0.06). dMMR was detected in 7.75% of all stages of CRCs, with the highest dMMR rate of 40% in stage II right-sided colon cancer. Conclusions: By assessing the mutations and clinical correlations of RAS and BRAF genes, and dMMR status, similar RAS mutation, dMMR frequency and lower BRAF mutation was observed in Chinese patients compared to western patients. A distinct molecular heterogeneity was found between patients with right-sided and left-sided CRCs.Keywords
This publication has 19 references indexed in Scilit:
- Racial Differences inBRAF/KRASMutation Rates and Survival in Stage III Colon Cancer PatientsJNCI Journal of the National Cancer Institute, 2015
- Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trialsAnnals of Oncology, 2014
- Interpreting the clinical utility of a pharmacogenomic marker based on observational association studiesThe Pharmacogenomics Journal, 2013
- BRAF mutation is a prognostic biomarker for colorectal liver metastasectomyJournal of Surgical Oncology, 2012
- Effect of KRAS Mutational Status in Advanced Colorectal Cancer on the Outcomes of Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: A Systematic Review and Meta-analysisClinical Colorectal Cancer, 2011
- Prognostic Role of KRAS and BRAF in Stage II and III Resected Colon Cancer: Results of the Translational Study on the PETACC-3, EORTC 40993, SAKK 60-00 TrialJournal of Clinical Oncology, 2010
- Genomic and Epigenetic Instability in Colorectal Cancer PathogenesisGastroenterology, 2008
- CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancerGut, 2008
- Prognostic Significance of Defective Mismatch Repair and BRAF V600E in Patients with Colon CancerClinical Cancer Research, 2008
- Association of Smoking, CpG Island Methylator Phenotype, and V600E BRAF Mutations in Colon CancerJNCI Journal of the National Cancer Institute, 2006