Oncotarget

Research Papers:

The molecular heterogeneity of sporadic colorectal cancer with different tumor sites in Chinese patients

Junjie Peng _, Dan Huang, Graeme Poston, Xiaoji Ma, Renjie Wang, Weiqi Sheng, Xiaoyan Zhou, Xiaoli Zhu and Sanjun Cai

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Oncotarget. 2017; 8:49076-49083. https://doi.org/10.18632/oncotarget.16176

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Abstract

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.


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