Reversed mutation rates of <i>KRAS</i> and <i>EGFR</i> genes in adenocarcinoma of the lung in Taiwan and their implications

Wu, Chun Ying; Hsu, Hui-Yu; Liu, Huiping; Chang, John Wen‐Cheng; Chen, Ya‐Ting; Hsieh, W.-Y.; Hsieh, Jia‐Juan; Hsieh, Meng-Long; Chen, Yirong; Huang, Shiu-Feng

doi:10.1002/cncr.23925

Cited by 83 publications

(78 citation statements)

References 157 publications

(150 reference statements)

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“…34,48 This was confirmed in our study. It is noteworthy that all KRAS mutations observed in our study were transition mutations and were not the transversion mutations more commonly observed in lung cancers from smokers.…”

Section: Discussionsupporting

confidence: 80%

Distinct clinical features and outcomes in never‐smokers with nonsmall cell lung cancer who harbor EGFR or KRAS mutations or ALK rearrangement

Kim

Shim

Chung

et al. 2011

Cancer

135

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BACKGROUND:The objectives of this study were to determine the proportions of major oncogenic alterations and to examine survival in genotype-specific subsets of never-smokers with nonsmall cell lung cancer (NSCLC). METHODS:The authors concurrently analyzed mutations in the epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) genes and investigated anaplastic lymphoma kinase (ALK) gene rearrangements in samples from 229 never-smokers with NSCLC. ALK rearrangements were identified by fluorescent in situ hybridization and were confirmed by immunohistochemistry. Mutations in EGFR (exons 18 to 21) and KRAS (codons 12 and 13) were determined by direct sequencing. RESULTS: Of 229 tumors, the frequency of EGFR mutations, ALK rearrangements, KRAS mutations, and no mutations (wild type [WT]) in any of the 3 genes (WT/WT/WT) was 48%, 8.3%, 3.5%, and 40.2%, respectively. All genetic alterations were mutually exclusive. The median progression-free survival after treatment with EGFR tyrosine kinase inhibitors (TKIs) was 12.8 months, 6.3 months, 2.1 months, and 1.6 months in patients with EGFR mutations, the WT/WT/WT genotype, KRAS mutations, and ALK rearrangements, respectively. In a Cox regression model, the adjusted hazard ratio for the risk of disease progression after treatment with EGFR TKIs was 0.59 (95% confidence interval [CI], 0.40-0.87; P ¼ .008) for patients with EGFR mutations, 4.58 (95% CI, 2.07-10.15; P < .001) for patients with ALK rearrangements, and 4.23 (95% CI, 1.65-10.8; P ¼ .003) for patients with KRAS mutations. Overall survival also differed significantly among genotypes. CONCLUSIONS: To the authors' knowledge, this was the largest comprehensive and concurrent analysis to date of 3 major oncogenic alterations in a cohort of East Asian never-smokers with NSCLC. Because survival outcomes differed among genotypes, and drugs that target specific alterations currently are available, genetic profiling to identify genotype-specific subsets can lead to successful treatment with appropriate kinase inhibitors. Cancer 2012;118:729

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Section: Discussionsupporting

confidence: 80%

Distinct clinical features and outcomes in never‐smokers with nonsmall cell lung cancer who harbor EGFR or KRAS mutations or ALK rearrangement

Kim

Shim

Chung

et al. 2011

Cancer

135

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“…Since their discovery two decades ago, KRAS mutations have been described in many types of human cancers with significantly different mutation frequency, including pancreas, colon, lung, breast and stomach cancer (4)(5)(6). High KRAS mutation frequency was found in many cancers such as pancreas, colon and lung cancer, whereas, gastric cancer has relatively low KRAS mutation frequency.…”

Section: Introductionmentioning

confidence: 99%

Mutation detection of KRAS by high-resolution melting analysis in Chinese with gastric cancer

Liu

Liu²,

Li³

et al. 2009

Oncol Rep

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Abstract. KRAS proteins play an important role in regulating cell functions. A series of studies has revealed that mutations of KRAS are involved in gastric carcinogenesis. However, mutation status of KRAS remains unclear in gastric cancer from Chinese Mainland. It has been proved that KRAS mutation associates with resistance to epidermal growth factor receptor (EGFR) inhibitors. In this study, KRAS mutations were detected in 52 gastric adenocarcinomas from Northern China. High-resolution melting analysis (HRMA) was used and positive samples were confirmed by direct sequencing. Of the 52 cancers, KRAS mutations were found in 5 (9.6%). All cancers with KRAS mutation were from male patients. Frequencies of KRAS mutation were 14.3% (3/21) and 6.5% (2/31) in differentiated and undifferentiated cancers; 25% (1/4) and 8.3% (4/48) in early and advanced wall penetration cancers; and were 13.3% (2/15) and 8.1% (3/37) in without and with lymph node metastasis cancers, respectively. There was no significant correlation between KRAS mutation and clinicopathological features. There were 3 mutation types in the 5 mutations, including 2 G12D, 1 G12V and 2 G13D mutations. All codon 12 mutations were found in patients with lymph node metastasis and at advanced stage, whereas all codon 13 mutations were found in patients without lymph node metastasis and at early stage. These results support KRAS mutation may only be involved in carcinogenesis of partial gastric cancers and the different mutation types of KRAS may take part in development of gastric cancer at different stages. The resistance of partial gastric cancer patients to EGFR inhibitors may be induced by KRAS mutation.

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“…Thus, its detection could be of clinical importance to the clinician in diagnosing and treating PA (Paez et al, 2004;Wu et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Co-amplification at Lower Denaturation-temperature PCR Combined with Unlabled-probe High-resolution Melting to Detect KRAS Codon 12 and 13 Mutations in Plasma-circulating DNA of Pancreatic Adenocarcinoma Cases

Zhou²,

Song³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: The aim of our study was to establish COLD-PCR combined with an unlabeled-probe HRM approach for detecting KRAS codon 12 and 13 mutations in plasma-circulating DNA of pancreatic adenocarcinoma (PA) cases as a novel and effective diagnostic technique. Materials and Methods: We tested the sensitivity and specificity of this approach with dilutions of known mutated cell lines. We screened 36 plasma-circulating DNA samples, 24 from the disease control group and 25 of a healthy group, to be subsequently sequenced to confirm mutations. Simultaneously, we tested the specimens using conventional PCR followed by HRM and then used target-DNA cloning and sequencing for verification. The ROC and respective AUC were calculated for KRAS mutations and/or serum CA 19-9. Results: It was found that the sensitivity of Sanger reached 0.5% with COLD-PCR, whereas that obtained after conventional PCR did 20%; that of COLD-PCR based on unlabeled-probe HRM, 0.1%. KRAS mutations were identified in 26 of 36 PA cases (72.2%), while none were detected in the disease control and/or healthy group. KRAS mutations were identified both in 26 PA tissues and plasma samples. The AUC of COLD-PCR based unlabeled probe HRM turned out to be 0.861, which when combined with CA 19-9 increased to 0.934. Conclusions: It was concluded that COLD-PCR with unlabeled-probe HRM can be a sensitive and accurate screening technique to detect KRAS codon 12 and 13 mutations in plasma-circulating DNA for diagnosing and treating PA.

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Reversed mutation rates of KRAS and EGFR genes in adenocarcinoma of the lung in Taiwan and their implications

Cited by 83 publications

References 157 publications

Distinct clinical features and outcomes in never‐smokers with nonsmall cell lung cancer who harbor EGFR or KRAS mutations or ALK rearrangement

Distinct clinical features and outcomes in never‐smokers with nonsmall cell lung cancer who harbor EGFR or KRAS mutations or ALK rearrangement

Mutation detection of KRAS by high-resolution melting analysis in Chinese with gastric cancer

Co-amplification at Lower Denaturation-temperature PCR Combined with Unlabled-probe High-resolution Melting to Detect KRAS Codon 12 and 13 Mutations in Plasma-circulating DNA of Pancreatic Adenocarcinoma Cases

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