Discordancy in BRAF mutations among primary and metastatic melanoma lesions: Clinical implications for targeted therapy

Joshua R. Bradish, Justin D. Richey, Kristin M. Post, Kari Meehan, Joyashree D. Sen, Amanda J. Malek, Terrence M. Katona, Simon Warren, Theodore F. Logan, Leslie A. Fecher, Liang Cheng

Research output: Contribution to journalArticle

20 Scopus citations


Systemic targeted molecular therapy, in the form of a selective BRAF inhibitor with or without a MEK inhibitor, is a standard treatment for patients with BRAF V600 mutation-positive melanoma with unresectable stage III and IV disease. Patients with BRAF mutation-negative primary tumors may manifest BRAF mutation-positive metastatic disease. It is unclear whether all metastatic lesions carry the same BRAF mutation status found in the primary tumor and if discordancy exists, in what frequency it occurs. Primary and matched metastatic lesions in 25 melanoma patients were tested for the BRAF V600E/Ec, V600K, V600D, and V600R mutations using a BRAF RGQ PCR kit (Qiagen). Four patients (16%) had discrepancies between their primary and metastatic melanoma BRAF status. Of these patients, 2 (8%) had BRAF mutation-positive primary melanomas with BRAF mutation-negative metastatic lesions and 2 (8%) patient had BRAF mutation-negative melanoma with a BRAF mutation-positive metastatic lesion. In summary, discordancy of BRAF mutation status is not an infrequent finding between primary and metastatic melanoma. It may be prudent in previously negative patients to determine BRAF mutation status of new metastatic tumors for proper allocation of BRAF inhibitor therapy. Discordant BRAF status may have a role in the varying patterns of response and inevitable resistance seen with BRAF inhibitor therapies.

Original languageEnglish (US)
Pages (from-to)480-486
Number of pages7
JournalModern Pathology
Issue number4
StatePublished - Apr 8 2015

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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