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BRAF and NRAS Mutations are Not Mutually Exclusive in Melanoma and in Single Melanoma Cells

BRAF and NRAS Mutations are Not Mutually Exclusive in Melanoma and in Single Melanoma Cells To the Editor: We read with interest the study by Chiappetta and colleagues reporting BRAF and NRAS mutational status intratumor heterogeneity within nodular melanomas. Using laser capture microdissection, they sampled and analyzed 3 different tumor areas in each of the 15 melanomas included in their study. Molecular analysis revealed different BRAF and NRAS mutations in at least 1 area in 7 of 11 BRAF -mutated or NRAS -mutated tumors. A tumor also contained 2 BRAFS467L and NRASQ61R mutations within the 3 sampled areas. 1 Considering tumor heterogeneity and possible BRAF and NRAS , double-mutants is very important for clinical management of patients with metastatic melanomas because this mutational status hardly influences the therapeutic strategy. BRAF and NRAS mutations were once considered as mutually exclusive in a same melanoma. Some studies have nevertheless reported cases of BRAF and NRAS double-mutated melanomas with a low incidence. 2–5 In our experience at the cancer molecular genetic platform of the Brest University Hospital, using pyrosequencing to search for BRAF codon 600 and NRAS codon 61 mutations in melanomas following the guidelines of the French Cancer Institute, we only identified a single case of double BRAFV600K and NRASQ61H mutant among 225 consecutive melanoma http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Applied Immunohistochemistry & Molecular Morphology Wolters Kluwer Health

BRAF and NRAS Mutations are Not Mutually Exclusive in Melanoma and in Single Melanoma Cells

BRAF and NRAS Mutations are Not Mutually Exclusive in Melanoma and in Single Melanoma Cells


To the Editor: We read with interest the study by Chiappetta and colleagues reporting BRAF and NRAS mutational status intratumor heterogeneity within nodular melanomas. Using laser capture microdissection, they sampled and analyzed 3 different tumor areas in each of the 15 melanomas included in their study. Molecular analysis revealed different BRAF and NRAS mutations in at least 1 area in 7 of 11 BRAF -mutated or NRAS -mutated tumors. A tumor also contained 2 BRAFS467L and NRASQ61R mutations within the 3 sampled areas. 1 Considering tumor heterogeneity and possible BRAF and NRAS , double-mutants is very important for clinical management of patients with metastatic melanomas because this mutational status hardly influences the therapeutic strategy. BRAF and NRAS mutations were once considered as mutually exclusive in a same melanoma. Some studies have nevertheless reported cases of BRAF and NRAS double-mutated melanomas with a low incidence. 2–5 In our experience at the cancer molecular genetic platform of the Brest University Hospital, using pyrosequencing to search for BRAF codon 600 and NRAS codon 61 mutations in melanomas following the guidelines of the French Cancer Institute, we only identified a single case of double BRAFV600K and NRASQ61H mutant among 225 consecutive melanoma samples (0.4%) The percentages of allelic mutations using next-generation sequencing (NGS) were 52.7% for BRAFV600K and 13.95% for NRASQ61H ( Fig. 1 ). These cases are albeit exceptional but not impossible. FIGURE 1 Primary superficial spreading melanoma of the arm in a 33-year-old woman. A, The biopsy comprised about 70% of tumor cells. B and C, Pyrosequencing analyses performed on formalin-fixed and paraffin-embedded tissue concluded in a BRAFV600K -mutated and NRASQ61H -mutated lesion. D, BRAFV600K allelic mutation percentage using next-generation sequencing (NGS) was 52.7%. E, NRASQ61H -mutated allelic mutation percentage using NGS was 13.95%. Pointing out an advance in...
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Copyright
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Subject
Online Articles: Letters to the Editor
ISSN
1541-2016
eISSN
1533-4058
DOI
10.1097/PAI.0000000000000217
pmid
26317309
Publisher site
See Article on Publisher Site

Abstract

To the Editor: We read with interest the study by Chiappetta and colleagues reporting BRAF and NRAS mutational status intratumor heterogeneity within nodular melanomas. Using laser capture microdissection, they sampled and analyzed 3 different tumor areas in each of the 15 melanomas included in their study. Molecular analysis revealed different BRAF and NRAS mutations in at least 1 area in 7 of 11 BRAF -mutated or NRAS -mutated tumors. A tumor also contained 2 BRAFS467L and NRASQ61R mutations within the 3 sampled areas. 1 Considering tumor heterogeneity and possible BRAF and NRAS , double-mutants is very important for clinical management of patients with metastatic melanomas because this mutational status hardly influences the therapeutic strategy. BRAF and NRAS mutations were once considered as mutually exclusive in a same melanoma. Some studies have nevertheless reported cases of BRAF and NRAS double-mutated melanomas with a low incidence. 2–5 In our experience at the cancer molecular genetic platform of the Brest University Hospital, using pyrosequencing to search for BRAF codon 600 and NRAS codon 61 mutations in melanomas following the guidelines of the French Cancer Institute, we only identified a single case of double BRAFV600K and NRASQ61H mutant among 225 consecutive melanoma

Journal

Applied Immunohistochemistry & Molecular MorphologyWolters Kluwer Health

Published: Mar 1, 2016

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