Deficient mismatch repair and <i>RAS</i> mutation in colorectal carcinoma patients: a retrospective study in Eastern China

Zhang, Xiangyan; Ran, Wenwen; Wu, Jie; Li, Hong; Liu, Hua‐Min; Wang, Lili; Xiao, Yujing; Wang, Xiaonan; Li, Yujun; Xing, Xiaoming

doi:10.7717/peerj.4341

Cited by 13 publications

(11 citation statements)

References 59 publications

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“…However, we observed that the age of high incidence of dMMR was different in different population studies. Our results are consistent with other studies of Chinese populations, with a high dMMR rate in young individuals . In studies of western populations, high dMMR rates appear to be associated with older age …”

Section: Discussionsupporting

confidence: 93%

Clinicopathologic features and prognostic value of KRAS, NRAS and BRAF mutations and DNA mismatch repair status: A single‐center retrospective study of 1,834 Chinese patients with Stage I–IV colorectal cancer

Guo

Tan

et al. 2019

Intl Journal of Cancer

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Mutations of KRAS, NRAS, BRAF and DNA mismatch repair (MMR) status have become an important part of the assessment of patients with colorectal cancer (CRC), while respective clinicopathologic features and prognostic significance in specific stages and related detection strategies remain unclear. We retrospectively analyzed clinicopathologic features and prognosis of 1,834 patients with Stage I–IV colorectal adenocarcinoma. Mutations in KRAS, NRAS and BRAF and DNA MMR status were determined. The mutation rates of KRAS, NRAS and BRAF were 46.4, 3.2 and 3.5%, respectively, and the mismatch repair gene deletion (dMMR) rate was 5.6%. In a multivariate analysis, female, advanced age, tumor type histology, mucinous carcinoma and positive tumor deposits were associated with a high KRAS mutation rate. A high BRAF mutation rate was associated with female, poor differentiation, lymphovascular invasion and positive tumor deposits. Factors associated with high dMMR rates included low age, large tumor size, poor differentiation, Stages I–III. Tumor site was independently associated with KRAS mutation, BRAF mutation and dMMR. KRAS and BRAF mutations were independent risk factors for shorter overall survival (OS) in Stage IV tumors but not in Stage I–III tumors. NRAS mutation was an independent risk factor for shorter OS in Stage I–II tumors. dMMR was independently associated with longer OS in Stage III tumors.

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Section: Discussionsupporting

confidence: 93%

Clinicopathologic features and prognostic value of KRAS, NRAS and BRAF mutations and DNA mismatch repair status: A single‐center retrospective study of 1,834 Chinese patients with Stage I–IV colorectal cancer

Guo

Tan

et al. 2019

Intl Journal of Cancer

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“…Association between KRAS mutation and mucinous histotype was reported in some studies [36,46,49] but denied in others [29,50,51], including ours.…”

Section: Discussionmentioning

confidence: 44%

“…Furthermore, Shen observed that these mutations were more frequent in distant metastasis tumors, and its rate varied with the different tumor stages [39]. Other studies did not find any correlations [29,36,37,49].…”

Section: Discussionmentioning

confidence: 93%

Clinicopathological characteristics and mutational profile of KRAS and NRAS in Tunisian patients with sporadic colorectal cancer

et al. 2021

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Background/aim: Colorectal cancer (CRC) is a major public health problem worldwide and in Tunisia due to its increasing incidence. KRAS and NRAS mutations have become a pivotal part of CRC diagnosis, given their association to treatment resistance with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies. We aim to screen for mutations in KRAS and NRAS genes in Tunisian patients with CRC and to explore their correlations with clinicopathological features. Materials and methods: AmoyDx KRAS and NRAS mutation real-time PCR kits were used to screen for mutations in KRAS (exon 2) and NRAS (exons 2, 3 and 4) in 96 CRC tumors. Results: KRAS exon 2 mutations were found in 41.7% (40/96) of the patients. Codon 12 most abundant mutations were G12D and G12V followed by G12A, while G13D is the predominant mutation in codon 13. KRAS exon 2 mutations were associated with older patients (p = 0.029), left-sided tumors (p = 0.037) and greater differentiation (p = 0.044). The prevalence rate of NRAS mutations was 7.3%, mostly in exon 2. These mutations were associated with early stages (p = 0.039) and the absence of lymph node metastasis (p = 0.045). Conclusion: It can be inferred from this study that Tunisian CRC patients have a similar frequency of KRAS and NRAS mutations compared to those observed in other populations. Consequently, screening for KRAS and NRAS mutation is crucial to orientate the therapies and the selection of an appropriate candidate, avoiding patients' unnecessary toxicity and costs.

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“…Patients who had undergone preoperative radiotherapy, chemotherapy and/or EGFR-targeted therapy were not included in this study. The clinic and pathologic variables were collected as previous description (Zhang et al, 2018a). The patients were followed up until December 2018, and the data concerning cancer recurrence and patient survival were collected.…”

Section: Methodsmentioning

confidence: 99%

HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China

Zhang

Wang

et al. 2020

PeerJ

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Objective To investigate the frequency and prognostic role of the human epidermal growth factor receptor 2 gene (HER2) and BRAF V600E gene mutation in Chinese patients with colorectal cancer (CRC). Methods Clinicopathological and survival information from 480 patients with stage I–III CRC were reviewed and recorded. HER2 amplification was analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), BRAF V600E mutation was tested by IHC and Sanger sequencing. The relationship between HER2 and BRAF V600E mutation status and clinicopathological characteristics and outcomes were determined. Results The amplification of HER2 and BRAF V600E mutation were identified in 27 of 480 (5.63%) and 19 of 480 (3.96%) CRC patients, respectively. HER2 amplification significantly correlated with greater bowel wall invasion (P = 0.041) and more advanced TNM stage (I vs. II vs. III; 0 vs 5.78% vs. 7.41%, P = 0.013). Patients suffering from tumors with poor differentiation had a higher incidence rate of BRAF V600E mutation than those with moderate/well differentiation (7.77% vs 2.92%, P = 0.04). HER2 amplification was an independent prognostic factor for worse disease-free survival (DFS) (HR = 2.53, 95% CI: 1.21–5.30, P = 0.014). Conclusion The prevalence of HER2 amplification and BRAF V600E mutation in stage I–III CRC patients in Chinese was 6% and 4%, respectively, and HER2 amplification appeared to be associated with a worse DFS. More comprehensive molecular classification and survival analysis are needed to validate our findings.

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Deficient mismatch repair and RAS mutation in colorectal carcinoma patients: a retrospective study in Eastern China

Cited by 13 publications

References 59 publications

Clinicopathologic features and prognostic value of KRAS, NRAS and BRAF mutations and DNA mismatch repair status: A single‐center retrospective study of 1,834 Chinese patients with Stage I–IV colorectal cancer

Clinicopathologic features and prognostic value of KRAS, NRAS and BRAF mutations and DNA mismatch repair status: A single‐center retrospective study of 1,834 Chinese patients with Stage I–IV colorectal cancer

Clinicopathological characteristics and mutational profile of KRAS and NRAS in Tunisian patients with sporadic colorectal cancer

HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China

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