Younger age at the time of first metastasis in BRAF-mutated compared to BRAF wild-type melanoma patients.

The relationship between BRAF mutations and the patient clinical profile is still under question. The objective of the present study was to correlate the BRAF mutation status in primary and metastatic melanomas with the clinicopathological profile, disease-free (DFS) and overall survival (OS). A total of 367 melanoma samples from 278 patients were screened for their BRAF status using a combination of allele-specific amplification and DNA sequencing. Two or three tissue samples from the same patient were available for 74 patients. The clinicopathological characteristics were tested for their association with the BRAF mutation using the Fisher's or Pearson's χ2 test. Log-rank tests and Cox models were used for survival analyses. BRAF mutation was found in 152 samples (41.4%). Ten of the 74 patients with several tissue samples (13.5%) had discordant BRAF mutation results. BRAF-mutated patients were significantly younger at the time of primary melanoma and first diagnosis of metastasis than BRAF wild-type patients but with no difference in DFS and OS. According to our results, a primary melanoma with BRAF mutation is not associated with a more aggressive illness.

[1]  N. Hayward,et al.  Prognostic value of BRAF mutations in localized cutaneous melanoma. , 2014, Journal of the American Academy of Dermatology.

[2]  B. Dréno,et al.  Is a single BRAF wild-type test sufficient to exclude melanoma patients from vemurafenib therapy? , 2014, The Journal of investigative dermatology.

[3]  E. Wardelmann,et al.  Assessment of clinical parameters associated with mutational status in metastatic malignant melanoma: a single‐centre investigation of 141 patients , 2013, The British journal of dermatology.

[4]  A. Hauschild,et al.  Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. , 2012, The Lancet. Oncology.

[5]  K. Flaherty,et al.  Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. , 2012, The New England journal of medicine.

[6]  Ardavan Saeedi,et al.  The Prognostic Value of BRAF Mutation in Colorectal Cancer and Melanoma: A Systematic Review and Meta-Analysis , 2012, PloS one.

[7]  J. Wilmott,et al.  Intratumoral Molecular Heterogeneity in a BRAF-Mutant, BRAF Inhibitor-Resistant Melanoma: A Case Illustrating the Challenges for Personalized Medicine , 2012, Molecular Cancer Therapeutics.

[8]  A. Hauschild,et al.  Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial , 2012, The Lancet.

[9]  J. Emile,et al.  Prognostic Value of BRAFV600 Mutations in Melanoma Patients After Resection of Metastatic Lymph Nodes , 2012, Annals of Surgical Oncology.

[10]  G. Botti,et al.  BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  Lauren E Haydu,et al.  Distinguishing Clinicopathologic Features of Patients with V600E and V600K BRAF-Mutant Metastatic Melanoma , 2012, Clinical Cancer Research.

[12]  M. Mazumdar,et al.  Intra- and Inter-Tumor Heterogeneity of BRAFV600EMutations in Primary and Metastatic Melanoma , 2012, PloS one.

[13]  A. Hauschild,et al.  Improved survival with vemurafenib in melanoma with BRAF V600E mutation. , 2011, The New England journal of medicine.

[14]  R. Scolyer,et al.  BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor, and the degree of solar elastosis at the primary tumor site , 2011, Pigment cell & melanoma research.

[15]  G. Mann,et al.  Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  J. Choi,et al.  Frequencies of BRAF and NRAS mutations are different in histological types and sites of origin of cutaneous melanoma: a meta‐analysis , 2011, The British journal of dermatology.

[17]  T. Saida,et al.  Polyclonality of BRAF mutations in primary melanoma and the selection of mutant alleles during progression , 2011, British Journal of Cancer.

[18]  R. Kefford,et al.  Targeting BRAF for patients with melanoma , 2010, British Journal of Cancer.

[19]  Li-E. Wang,et al.  Clinical Correlates of NRAS and BRAF Mutations in Primary Human Melanoma , 2010, Clinical Cancer Research.

[20]  Jeffrey E Gershenwald,et al.  Final version of 2009 AJCC melanoma staging and classification. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  Jane Fridlyand,et al.  Improving Melanoma Classification by Integrating Genetic and Morphologic Features , 2008, PLoS medicine.

[22]  M. Denis,et al.  Real-time allele-specific amplification for sensitive detection of the BRAF mutation V600E. , 2004, Molecular and cellular probes.

[23]  J. Becker,et al.  Constitutive activation of the Ras-Raf signaling pathway in metastatic melanoma is associated with poor prognosis , 2004, Journal of carcinogenesis.

[24]  D. Morton,et al.  Incidence of BRAF Oncogene Mutation and Clinical Relevance for Primary Cutaneous Melanomas , 2004, Clinical Cancer Research.

[25]  A. Nicholson,et al.  Mutations of the BRAF gene in human cancer , 2002, Nature.

[26]  L. Schwartz,et al.  New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). , 2009, European journal of cancer.