High concordance of BRAF mutational status in matched primary and metastatic melanoma

Cormican, David; Kennedy, Ciaran R.; Murphy, Sandra; Werner, Réiltín; Power, Derek G.; Heffron, Cynthia

doi:10.1111/cup.13393

Cited by 12 publications

(13 citation statements)

References 37 publications

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“…In our cohort, the concordance rates of BRAF, C-KIT, and NRAS mutations between paired primary and metastatic lesions were 94.0%, 97.7%, and 94.9% respectively. A recent study conducted by Cormican et al showed the high concordance of BRAF mutational status in matched primary and metastatic melanoma (52/53, 98%) 30 , which was higher than the results in our study. However, the study conducted by Manca et al revealed that mutational concordance in pathogenic/pathogenic like mutations between primary and metastatic melanoma was only 76% 6 , even different site from the same lesion could exist diverse genetic alterations [32][33][34] .…”

Section: Discussioncontrasting

confidence: 99%

BRAF, C-KIT, and NRAS mutations correlated with different clinicopathological features: an analysis of 691 melanoma patients from a single center

Ren

Zhang

Kong

et al. 2021

Preprint

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Aims To analyze the prevalence and relevance of pathogenetic mutations in BRAF, C-KIT, and NRAS in Chinese melanoma patients to provide some potential reference for the targeted treatment in China. Methods We described the frequency and distribution of BRAF, NRAS, and C-KIT mutation in 691 melanoma patients, and analyze the statistical significance of different gene mutation with clinicopathological features. Results BRAF mutation was found in 166 patients (24.0%), and V600E was the prominent genetic alteration (87.3%). Statistical analysis showed that younger patients had a higher BRAF mutation rate than the older. Furthermore, the frequency of BRAF mutation in patients with extremity location, ALM type, thinner thickness and no ulceration was more likely to be lower. The rate of NRAS mutation was 12.6% (38/302), mainly involved codon 61 in exon 3 and codon 12 in exon 2. C-KIT mutation was detected in 65 patients (9.4%), and the most common sites of mutations was L576 in exon 11 (44.6%). Patients with NRAS or C-KIT mutation had higher Clark level and more likely to be located in extremity than those without mutation. The concordance of BRAF, NRAS, and C-KIT mutations between paired primary and metastatic lesions was 89.6% (60/67), and visceral metastases showed a highest similar distribution of gene mutations versus primary melanomas compared with lymph nodes and cutaneous metastases. Conclusions In this large cohort on Chinese population, the frequency of BRAF and NRAS mutation was relatively lower than that in Caucasian, but the clinicopathological features of BRAF, C-KIT and NRAS mutation were similar. Paired primary and metastatic lesions showed high concordance of gene mutations.

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Section: Discussioncontrasting

confidence: 99%

BRAF, C-KIT, and NRAS mutations correlated with different clinicopathological features: an analysis of 691 melanoma patients from a single center

Ren

Zhang

Kong

et al. 2021

Preprint

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“…Several previous studies have described the heterogeneity of genetic alterations between primary and corresponding metastatic lesions in melanoma (19,(29)(30)(31). In our cohort, the concordance rates of BRAF, C-KIT, and NRAS mutations between paired primary and metastatic lesions were 94.0%, 97.7%, and 94.9%, respectively.…”

Section: Discussionsupporting

confidence: 50%

BRAF, C-KIT, and NRAS mutations correlated with different clinicopathological features: an analysis of 691 melanoma patients from a single center

Ren¹,

Zhang²,

Kong³

et al. 2022

Ann Transl Med

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Background: Discrepancies in genetic alterations found in melanoma are conspicuous between different ethnic groups. With the approval of BRAF-and MEK-targeted inhibitors in China, it is necessary to further elucidate the landscape of gene mutation in Chinese melanoma patients. Methods:The frequency and distribution of BRAF, C-KIT, and NRAS mutations in 691 melanoma patients was determined, and the statistical significance of correlations between different gene mutations and clinicopathological features was analyzed.Results: Among a total of 691 patients, BRAF mutation was found in 166 patients (24.0%), and V600E was the prominent genetic alteration (145/166, 87.3%). Statistical analyses showed that younger patients (<60) had a higher BRAF mutation rate than older patients (≥60, P=0.000), and the frequency of BRAF mutation was more likely to be lower in patients with the following: melanoma located in an extremity (P=0.000), acral-lentiginous melanoma subtype (P=0.000), thinner melanoma thickness (P=0.047), and no ulceration (P=0.030). The frequency of NRAS mutation was 12.6% (38/302), and primarily involved codon 61 in exon 3 and codon 12 in exon 2. Mutation of C-KIT was detected in 65 patients (9.4%), and the most common site of mutations was L576 in exon 11 (29/65, 44.6%). Patients with NRAS or C-KIT mutation had higher Clark level (P=0.035 and 0.047, respectively) and were more likely to have melanoma located in an extremity (P=0.003 and 0.009, respectively) than those without such mutation. The concordance of gene mutations between paired primary and metastatic lesions was 89.6% (60/67), and visceral metastases showed the highest distribution of gene mutations versus primary melanomas (100.0%) compared with lymph nodes (90.9%) and cutaneous metastases (83.3%). Conclusions:In this large cohort of Chinese melanoma patients, the frequencies of BRAF and NRAS mutations were lower than those observed in Caucasian cohorts, but the clinicopathological features of BRAF, C-KIT, and NRAS mutation were consistent. Paired primary and metastatic lesions showed high concordance of gene mutations.

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“…In the metastatic setting, it is recommended to perform molecular analyses in metastatic sample, if available, because it represents the most recent lesion and it is often composed by a large majority of neoplastic cells. When a metastatic tissue sample is not available, the analyses may be performed on samples obtained from lymph node metastases or primary tumor since a high concordance of the BRAF status between primary melanomas and their metastatic lesions has been demonstrated (Colombino et al, 2012 ; Casula et al, 2016 ; Valachis and Ullenhag, 2017 ; Cormican et al, 2019 ; Pellegrini et al, 2020 ). Additionally, the NCCN clinical practice guidelines recommend BRAF mutation testing in patients with resectable and unresectable or metastatic melanoma to guide treatment decisions (NCCN Clinical Practice Guidelines in Oncology 3 )?…”

Section: Molecular Backgroundmentioning

confidence: 99%

The Current State of Molecular Testing in the BRAF-Mutated Melanoma Landscape

Vanni

Tanda

Spagnolo

et al. 2020

Front. Mol. Biosci.

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The incidence of melanoma, among the most lethal cancers, is widespread and increasing. Metastatic melanoma has a poor prognosis, representing about 90% of skin cancer mortality. The increased knowledge of tumor biology and the greater understanding of the immune system role in the anti-tumor response has allowed us to develop a more rational approach to systemic therapies. The discovery of activating BRAF mutations in half of all melanomas has led to the development of molecularly targeted therapy with BRAF and MEK inhibitors, which dramatically improved outcomes of patients with stage IV BRAF-mutant melanoma. More recently, the results of clinical phase III studies conducted in the adjuvant setting led to the combined administration of BRAF and MEK inhibitors also in patients with resected high-risk melanoma (stage III). Therefore, BRAF mutation testing has become a priority to determine the oncologist's choice and course of therapy. In this review, we will report the molecular biology-based strategies used for BRAF mutation detection with the main advantages and disadvantages of the most commonly used diagnostic strategies. The timing of such molecular assessment in patients with cutaneous melanoma will be discussed, and we will also examine considerations and approaches for accurate and effective BRAF testing.

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High concordance of BRAF mutational status in matched primary and metastatic melanoma

Cited by 12 publications

References 37 publications

BRAF, C-KIT, and NRAS mutations correlated with different clinicopathological features: an analysis of 691 melanoma patients from a single center

BRAF, C-KIT, and NRAS mutations correlated with different clinicopathological features: an analysis of 691 melanoma patients from a single center

BRAF, C-KIT, and NRAS mutations correlated with different clinicopathological features: an analysis of 691 melanoma patients from a single center

The Current State of Molecular Testing in the BRAF-Mutated Melanoma Landscape

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