A detailed analysis of K-ras point mutations in relation to tumor progression and survival in colorectal cancer patients

Span, Mary; Moerkerk, Peter T.M.; Goeli, Anton F. P. M. De; Arends, Jan Willem

doi:10.1002/(sici)1097-0215(19960621)69:3<241::aid-ijc15>3.0.co;2-a

Cited by 90 publications

(14 citation statements)

References 23 publications

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“…The reported frequency of KRAS mutation has ranged from 29.6% 26 to 65% 27 depending on the methods. In this study, the KRAS mutation rate was 60% in the clinical samples by PCqP-CR which was in close concordance with the rate reported by Span et al 27 (65%) with nested PCR followed by single-strand conformation polymorphism, and Tsiatis et al 17 reported a KRAS mutation rate of 61.6% by pyrosequencing. However, the mutation rate in this study is much higher than 32.1% reported by Kobunai et al 19 who applied the same strategy that we used.…”

Section: Discussionsupporting

confidence: 91%

Rapid and Sensitive Detection ofKRASMutation by Peptide Nucleic Acid-based Real-time PCR Clamping: A Comparison with Direct Sequencing between Fresh Tissue and Formalin-fixed and Paraffin Embedded Tissue of Colorectal Cancer

Jeong

Lee

et al. 2011

Korean J Pathol

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Background: Rapid and sensitive detection of KRAS mutation is needed to maximize the benefits for patients who are being treated with monoclonal antibodies to target the epidermal growth factor receptor in colorectal cancer. The aim of this study is to evaluate the efficacy of the peptide nucleic acid clamp real-time PCR (PCqPCR) as compared to that of direct sequencing (DS) between using fresh colorectal cancer tissue and the matched formalin-fixed and paraffin-embedded (FFPE) colorectal cancer tissue. Methods: The efficacy of PCqPCR was evaluated and compared with that of DS using fresh tissue and matched FFPE tissue from 30 cases of colorectal cancer. Results: PCqPCR is more sensitive than DS for detecting KRAS mutation. PCqPCR detected 1% of mutants in 1 ng DNA. PCqPCR detected mutation in 1% of mutant cells, while DS barely detected, by manual reading, that in 20-50% of mutant cells. In the clinical samples, PC-qPCR detected KRAS mutation in 60.0% while DS detected KRAS mutation in 53.3% of the colorectal cancers. The two methods showed a 100% concordance rate for detecting KRAS mutation between the fresh tissue and FFPE tissue. Conclusions: The PCqPCR method is efficiently applicable for the detection of KRAS mutation in a clinical setting.

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Section: Discussionsupporting

confidence: 91%

Rapid and Sensitive Detection ofKRASMutation by Peptide Nucleic Acid-based Real-time PCR Clamping: A Comparison with Direct Sequencing between Fresh Tissue and Formalin-fixed and Paraffin Embedded Tissue of Colorectal Cancer

Jeong

Lee

et al. 2011

Korean J Pathol

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“…The incidence of K/NRAS mutation in our cohort was 43%, which was higher than prior studies of hepatic metastasectomy, 14,19 but in line with other reports of metastatic lesions. 17,18 In our more in-depth investigation of the K/NRAS gene, approximately 20% of these mutations occurred in less common locations on exons 3 and 4. This is important, because these mutations are often excluded from traditional mutational analysis.…”

Section: Discussionmentioning

confidence: 94%

Mutation location on the RAS oncogene affects pathologic features and survival after resection of colorectal liver metastases

Frankel

Vakiani

Nathan

et al. 2016

Cancer

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BACKGROUND In the past 3 decades, a better understanding of gene mutations and their role in carcinogenesis has led to improvement in our ability to treat patients with metastatic disease. The objective of the current study was to determine whether the location of a driver mutation within an affected gene impacts the biology of metastatic colorectal cancer. METHODS DNA was collected from 165 randomly selected specimens of patients who underwent margin-negative resection of colorectal liver metastases with curative intent. Sequenom analysis and Sanger sequencing were used to evaluate mutations in K/NRAS, PIK3CA, BRAF, and TP53. RESULTS BRAF mutation was associated with early recurrence and death, whereas no impact of TP53 or PIK3CA mutation was identified. Although K/NRAS mutation was associated with worse survival in this cohort, this difference was no longer evident when those who had received anti-EGFR therapy were excluded. When stratifying patients according to the exon on which K/NRAS was mutated, there were dramatic differences in both survival and pathologic features. Exon 4 mutations were associated with large, solitary metastases occurring at long disease-free intervals compared with exon 3 mutations, which presented with small, numerous lesions. Patients who had exon 4 mutations recurred infrequently and had significantly longer survival compared with those who had wild type or other mutations. CONCLUSIONS By using this model of curative-intent, margin-negative resection in patients at high risk of recurrence, the authors were able to establish a link between mutation location within the K/NRAS gene and the biology of metastatic colorectal cancer.

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“…It was demonstrated that patients with G>A mutations and G>C mutations tended to have a worse prognosis than those with G>T mutations. 28 In addition, it was found that the presence of KRAS mutations increased risk of recurrence and death. In particular, any mutation of G>T but not G>A or G>C increased the risk of recurrence and death.…”

Section: Discussionmentioning

confidence: 99%

KRAS G>A mutation favors poor tumor differentiation but may not be associated with prognosis in patients with curatively resected duodenal adenocarcinoma

Guzzetta

Jeschke

et al. 2013

Intl Journal of Cancer

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KRAS mutations have been found in duodenal adenocarcinomas and may have prognostic significance. The purpose of this study was to classify clinicopathological characteristics, microsatellite instability, and KRAS mutations and identify possible prognostic role of KRAS mutations in duodenal adenocarcinomas. Demographics, tumor characteristics and survival were recorded for 78 patients with duodenal adenocarcinomas (stages I to III). KRAS mutations were detected in 27 (34.6%) cases, of which the majority (74.1%) were G>A transitions. Multivariate logistic regression analysis showed that KRAS G>A mutation was significantly associated with late stage (p = 0.025) and poor tumor differentiation (p = 0.035), when compared with wild-type and other than G>A mutations. KRAS G>A mutation carriers were at increased risk for distant relapse (p = 0.022) and had significantly shorter overall survival (OS; log-rank p = 0.045) and a trend toward shorter relapse-free survival (RFS; log-rank p = 0.062) when compared with those who did not carry the KRAS G>A mutation. In multivariate analyses, there was a significant correlation between ≥ 3 positive lymph nodes and poor OS (p < 0.001) and RFS (p = 0.001) and KRAS G>A mutation carriers demonstrated no effect on clinical outcome. In conclusion, KRAS G>A mutation correlates significantly with late stage and poor tumor differentiation in duodenal adenocarcinoma. Among patients who undergo a curative resection of duodenal adenocarcinoma, KRAS G>A mutation carriers will more likely experience distant relapse but may not exhibit a poor prognosis. Number of positive lymph nodes should be incorporated in future staging systems.

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A detailed analysis of K-ras point mutations in relation to tumor progression and survival in colorectal cancer patients

Abstract: o 1996 Wiley-Liss, Inc.

Cited by 90 publications

References 23 publications

Rapid and Sensitive Detection ofKRASMutation by Peptide Nucleic Acid-based Real-time PCR Clamping: A Comparison with Direct Sequencing between Fresh Tissue and Formalin-fixed and Paraffin Embedded Tissue of Colorectal Cancer

Rapid and Sensitive Detection ofKRASMutation by Peptide Nucleic Acid-based Real-time PCR Clamping: A Comparison with Direct Sequencing between Fresh Tissue and Formalin-fixed and Paraffin Embedded Tissue of Colorectal Cancer

Mutation location on the RAS oncogene affects pathologic features and survival after resection of colorectal liver metastases

KRAS G>A mutation favors poor tumor differentiation but may not be associated with prognosis in patients with curatively resected duodenal adenocarcinoma

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