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Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma
Published on: September 8, 2021
Rare BRAF mutations in melanoma patients: implications for molecular testing in clinical practice
L Heinzerling1, S Kühnapfel, D Meckbach
1Department of Dermatology, University Hospital Erlangen, 91052 Erlangen, Germany. lheinzer@post.harvard.edu
Background:
The detection of V600E BRAF mutation in melanoma is fundamental since here BRAF inhibitors represent an effective treatment. Non-V600E BRAF mutations that may also respond are not detected by certain screening methods. Thus, knowledge about detection of these mutations is needed.
Methods:
A total of 276 tumour samples from 174 melanoma patients were investigated for BRAF mutations by pyrosequencing. Rare mutations were confirmed by capillary sequencing and compared with findings from COBAS test and immunohistochemistry using a novel BRAF antibody. Melanoma type, localisation, and survival were summarised.
Results:
BRAF mutations were found in 43% of patients (124 tumours in 75 patients). Among those, 14 patients (18.7%) exhibited rare mutations. The V600EK601del and V600DK601del mutations have never been described before in melanoma. Furthermore, V600K, V600E2, and V600D, V600G, V600R, and L597S mutations were detected. Mutations were not detected by COBAS test in 7 out of these 14 patients and immunohistochemistry only reliably detected patients with the V600E2 and V600EK601del mutation.
Conclusion:
Accurate diagnosis of rare BRAF mutations is crucial. We show that pyrosequencing is accurate, highly sensitive, reliable, and time saving to detect rare BRAF mutations. Missing these rare variant mutations would exclude a subset of patients from available effective BRAF-targeting therapy.
Insights
Accurate detection of rare BRAF mutations in melanoma is crucial for effective BRAF-inhibitor therapy. Pyrosequencing reliably identifies these mutations, ensuring more patients receive life-saving treatments.
Area of Science:
- Oncology
- Genetics
- Dermatology
Background:
- BRAF mutations are key targets for melanoma treatment.
- Standard screening methods may miss non-V600E BRAF mutations.
- Identifying all BRAF variants is essential for patient management.
Purpose of the Study:
- To evaluate pyrosequencing for detecting rare BRAF mutations in melanoma.
- To compare pyrosequencing with other diagnostic methods.
- To highlight the clinical significance of identifying rare BRAF mutations.
Main Methods:
- Investigated 276 melanoma tumor samples from 174 patients for BRAF mutations using pyrosequencing.
- Confirmed rare mutations via capillary sequencing.
- Compared pyrosequencing results with COBAS test and immunohistochemistry.
Main Results:
- BRAF mutations detected in 43% of patients; 18.7% had rare mutations.
- Identified novel V600EK601del and V600DK601del mutations.
- Pyrosequencing detected mutations missed by COBAS test and immunohistochemistry in several cases.
Conclusions:
- Accurate diagnosis of rare BRAF mutations is critical for melanoma treatment.
- Pyrosequencing is a sensitive, reliable, and efficient method for detecting rare BRAF mutations.
- Failure to detect rare variants may deny patients effective BRAF-targeting therapies.
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