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Oncotarget. 2017 Jul 25;8(30):49076-49083. doi: 10.18632/oncotarget.16176.

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

Peng J1,2, Huang D2,3, Poston G4, Ma X1,2, Wang R1,2, Sheng W2,3, Zhou X2,3, Zhu X2,3, Cai S1,2.

Author information

1
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
2
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
3
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
4
Department of Surgery, Aintree University Hospital, Liverpool L9 7AL, UK.

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:

BRAF; RAS; colorectal cancer; heterogeneity; mutation

PMID:
28416767
PMCID:
PMC5564750
DOI:
10.18632/oncotarget.16176
[Indexed for MEDLINE]
Free PMC Article

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