Prevalence of BRAF V600E mutation in Chinese melanoma patients: Large scale analysis of BRAF and NRAS mutations in a 432-case cohort

Si, Lu; Kong, Yan; Xu, Xiaowei; Flaherty, Keith T.; Sheng, Xinan; Cui, Chuanliang; Chen, Zhihong; Li, Siming; Mao, Lili; Guo, Jun

doi:10.1016/j.ejca.2011.06.056

Cited by 210 publications

(201 citation statements)

References 32 publications

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“…Among RAS mutations, NRASQ61R is the most common in the majority of studies. [11][12][13][14][15] These results have been recently confirmed by a retrospective analysis in a large cohort of patients with advanced melanoma who underwent testing for both BRAF (exon 15) and NRAS (exons 1 and 2) mutations. 5 Finally, it is important to underline that NRASQ61R has been reported to correlate with resistance to BRAF inhibitors in preclinical and clinical data.…”

Section: Discussionmentioning

confidence: 68%

Immunohistochemistry is highly sensitive and specific for the detection of NRASQ61R mutation in melanoma

et al. 2015

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Testing for NRAS is now integral part in the assessment of metastatic melanoma patients because there is evidence that NRAS-mutated patients may be sensitive to MEK inhibitors, and RAS mutation is a common mechanism of acquired resistance during treatment with BRAF inhibitors. This study evaluated the sensitivity and specificity of immunohistochemical analysis using an N-Ras (Q61R) antibody to detect the presence of the NRASQ61R mutation in melanoma patients. A total of 98 primary cutaneous melanomas that have undergone examination of NRAS mutation were retrieved from a multicentric database. Formalin-fixed and paraffin-embedded melanoma tissues were analyzed for BRAF and NRAS mutations by independent, blinded observers using both conventional DNA molecular techniques and immunohistochemistry with the novel anti-human N-Ras (Q61R) monoclonal antibody (clone SP174). The antibody showed a sensitivity of 100% (14/14) and a specificity of 100% (83/83) for detecting the presence of an NRASQ61R mutation. Of the NRAS-mutated cases, none of the non-Q61R cases stained positive with the antibody (0/7). There were three cases with discordant NRAS mutational results. Additional molecular analysis confirmed the immunohistochemically obtained NRAS result in all cases, suggesting that a multiple analytical approach can be required to reach the correct sample classification. The reported immunohistochemical method is an accurate, rapid, and cost-effective method for detecting NRASQ61R mutation in melanoma patients, and represents a valuable supplement to traditional mutation testing. If validated in further studies, genetic testing would only be required for immunohistochemistry-negative patients to detect non-Q61R mutations.

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Section: Discussionmentioning

confidence: 68%

Immunohistochemistry is highly sensitive and specific for the detection of NRASQ61R mutation in melanoma

et al. 2015

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“…Studies involving China, Korea and Japan revealed that there may be some differences in incidence of melanoma compared with the findings in Caucasians, including frequency and an age association with BRAF mutation 7, 8, 9, 10. In a recent study conducted in Japan, the detection rates of BRAF , NRAS and KIT mutations were 30.4%, 12.3% and 12.9%, respectively 11…”

Section: Introductionmentioning

confidence: 96%

Phase 1/2 study assessing the safety and efficacy of dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation‐positive advanced cutaneous melanoma

Yamazaki¹,

Tsutsumida²,

Takahashi³

et al. 2018

The Journal of Dermatology

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The combination of dabrafenib and trametinib demonstrated encouraging antitumor activity and tolerability, at initial analysis, in Japanese patients with BRAF V600 mutant advanced melanoma warranting further investigation. This study evaluated the safety and tolerability, pharmacokinetics (PK) and preliminary efficacy of dabrafenib 150 mg b.i.d. plus trametinib 2 mg q.d. in Japanese patients with BRAF V600E/K mutant solid tumors (phase 1) and melanoma (phase 2). Phase 1 was primarily intended to assess safety and tolerability as assessed by adverse events (AE), and the primary end‐point in phase 2 was to assess confirmed overall response rate (ORR). The secondary end‐points in phase 1 included PK, confirmed/unconfirmed ORR and duration of response (DOR). The secondary end‐points in phase 2 were PK, unconfirmed ORR, DOR, safety and tolerability. A total of 12 cutaneous melanoma patients were enrolled in the study (six in phase 1 and six in phase 2) and received the combination therapy of dabrafenib and trametinib. Common AE (≥50.0%) included pyrexia (75%), increased aspartate aminotransferase (67%), peripheral edema (50%) and nasopharyngitis (50%). The investigator‐assessed ORR was reported in five patients (83%) in phase 1 and was also reported in five patients (83%; 95% confidence interval, 35.9–99.6; P < 0.0001) in phase 2. Plasma concentrations of both dabrafenib and trametinib seemed to a reach steady state by week 3. Overall, efficacy and PK properties for the dabrafenib plus trametinib combination in Japanese patients were comparable with those seen in global studies.

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“…Another study on primary nasal MM showed that 55.2% of MM patients had p16 INK4A depletion (164). Gene testing for over 100 Chinese MM patients showed that the mutation rates of KIT, BRAF, and NRAS genes were was 19.2%, 12.5%, and 9.2%, respectively (10,11). Multivariate analysis showed KIT mutation was an independent prognostic factor of MM, with a hazard ratio of 2.696 (95% CI: 1.204−6.038) (P=0.016).…”

Section: Genesmentioning

confidence: 99%

“…Detection of BRAF gene in 468 Chinese patients with primary melanoma showed that the BRAF mutation rate was 25.9%; specifically, the BRAF mutation rate was 17.9% and 12.5% in acral type and mucosal type, among which V600E is the most common mutation site (87.6%). The findings of this study provided theoretical basis for the use of BRAF V600 inhibitors in Chinese melanoma patients (10,11).…”

Section: Acral Lentiginous Melanomamentioning

confidence: 99%

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Chinese Guidelines on the Diagnosis and Treatment of Melanoma (2015 Edition)

et al. 2016

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Prevalence of BRAF V600E mutation in Chinese melanoma patients: Large scale analysis of BRAF and NRAS mutations in a 432-case cohort

Cited by 210 publications

References 32 publications

Immunohistochemistry is highly sensitive and specific for the detection of NRASQ61R mutation in melanoma

Immunohistochemistry is highly sensitive and specific for the detection of NRASQ61R mutation in melanoma

Phase 1/2 study assessing the safety and efficacy of dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation‐positive advanced cutaneous melanoma

Chinese Guidelines on the Diagnosis and Treatment of Melanoma (2015 Edition)

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