Clinicopathological features of nonsmall cell lung carcinomas with BRAF mutations

Kinno, Tomoaki; Tsuta, Koji; Shiraishi, Kouya; Mizukami, Takuro; Suzuki, Mikiko; Yoshida, Akihiko; Suzuki, Kenji; Asamura, Hisao; Furuta, Koh; Kohno, Takashi; Kushima, Ryoji

doi:10.1093/annonc/mdt495

Cited by 122 publications

(113 citation statements)

References 21 publications

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“…study revealed an incidence of non-V600E BRAF mutations of 83.3% (10/12), similar to that demonstrated by NGS studies (17,61,63). Of the 10 non-V600E-mutated patients in the present study, 75.0% (9/12) carried D594G and 8.3% (1/12) carried G469A, so the mutation rates were may be represented as D594G>V600E>G469A, which is concordant with the results obtained by Carter et al (17).…”

Section: Discussionsupporting

confidence: 92%

“…Prior studies revealed that BRAF and EGFR mutations are exclusive in NSCLC (66)(67)(68) This phenomenon seems plausible since BRAF mutation was demonstrated as one of the mechanisms of resistance to EGFR-TKIs (69). However, concurrent BRAF and EGFR mutations were observed in further studies (61,70). Among the 7 BRAF+EGFR mutation-positive patients in the present study, all of their BRAF mutations were D594G; the BRAF mutations in the BRAF+EGFR mutation-positive patients in other studies were also non-V600E (61,70).…”

Section: Discussioncontrasting

confidence: 42%

“…However, concurrent BRAF and EGFR mutations were observed in further studies (61,70). Among the 7 BRAF+EGFR mutation-positive patients in the present study, all of their BRAF mutations were D594G; the BRAF mutations in the BRAF+EGFR mutation-positive patients in other studies were also non-V600E (61,70). Of the aforementioned BRAF mutations, V600E is the only kinase-activating one and could result in the activation of downstream mitogen-activated protein kinase kinase-extracellular signal-regulated kinase signaling pathway resistance to EGFR-TKIs (71).…”

Section: Discussionmentioning

confidence: 87%

“…The BRAF gene is mutated in 1-5% of NSCLC cases, and the majority of these are mutated in adenocarcinomas (17,18,61,62). When NGS was used, the incidence of BRAF mutation appeared to be 6.5% (33/510) (63).…”

Section: Discussionmentioning

confidence: 99%

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Detection of EGFR and BRAF mutations by competitive allele-specific TaqMan polymerase chain reaction in lung adenocarcinoma

et al. 2017

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Abstract. Epithelial growth factor receptor (EGFR)-tyrosine kinase inhibitors are the standard first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) expressing sensitive EGFR-mutants. Other drugs target different driver mutants, including the serine/threonine-protein kinase B-raf (BRAF) inhibitor dabrafenib, which has exhibited promising efficacy for treating patients with metastatic BRAF-mutated NSCLC. Therefore, identifying patients carrying mutations that may be treated using targeted therapies is important. However, the methods of molecular detection presently applied in clinical practice, particularly detection of BRAF in NSCLC patients, require further investigation. Therefore, more sensitive and economic methods are required. The present study applied the competitive allele-specific TaqMan polymerase chain reaction (CastPCR) technology to the molecular detection of EGFR (del2235-2249, del2236-2250, T790M, L858R) and BRAF (V600E, G469A, D594G) mutations in 144 treatment-naive patients with lung adenocarcinoma, and analyzed the association between the mutation rates and patients' clinicopathological features. 51.4% (74/144) cases were identified harboring EGFR mutations. A total of 40.3% (58/144) patients carried sensitizing mutations (exon 19 deletion or L858R) and 14.6% (21/144) carried T790M mutations. 6.9% (10/144) mutation-positive patients were double-mutated. Total EGFR mutation rate was significantly increased in female compared with that of males (60.9 vs. 43.8%, P<0.05), in non-smokers compared with that of smokers (62.8 vs. 34.5%, P<0.05). In total, 8.3% (12/144) patients were identified with BRAF mutations. 16.7% were V600E (2/12) and 83.3% (10/12) were non-V600E mutants. Among the 10 non-V600E mutations, D594G accounted for 90.0% (9/10) and G469A accounted for 10.0% (1/10). Statistical analysis demonstrated that the BRAF mutation rate was not associated with any of the following clinicopathological features: Sex, age, smoking history, clinical stages, distant metastasis, differentiation degree, tumor size and regional lymph node metastasis (P≥0.05). CastPCR technology is a robust method with high sensitivity for the molecular detection of EGFR and BRAF mutations in clinical formalin-fixed paraffin-embedded samples.

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Section: Discussionsupporting

confidence: 92%

Section: Discussioncontrasting

confidence: 42%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Detection of EGFR and BRAF mutations by competitive allele-specific TaqMan polymerase chain reaction in lung adenocarcinoma

et al. 2017

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“…BRAF p.V600E mutation is more frequent in females 52,54 and never smokers 54 in some studies, but several studies failed to show these associations. 49,50,53,58 One distinction between BRAF mutations and other Figure 1 Forest plot of sensitivity and specificity for immunohistochemistry (IHC)-based determination of ROS1 rearrangement positivity compared with fluorescence in situ hybridization. Pooled estimate of sensitivity and specificity based on bivariate analysis of included studies.…”

Section: Expert Consensus Opinionmentioning

confidence: 99%

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

Aung

Donald

Ellison

et al. 2014

The Journal of Molecular Diagnostics

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Context: In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. Objective: To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update. Design: The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations. Results: Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline. Conclusions: The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of

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RAS‐RAF‐MEK Pathway: Aberrations and Therapeutic Possibilities

Muñoz

Janků

2015

Targeted Therapy in Translational Cancer Research

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Clinicopathological features of nonsmall cell lung carcinomas with BRAF mutations

Cited by 122 publications

References 21 publications

Detection of EGFR and BRAF mutations by competitive allele-specific TaqMan polymerase chain reaction in lung adenocarcinoma

Detection of EGFR and BRAF mutations by competitive allele-specific TaqMan polymerase chain reaction in lung adenocarcinoma

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

RAS‐RAF‐MEK Pathway: Aberrations and Therapeutic Possibilities

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