Discordancy in BRAF mutations among primary and metastatic melanoma lesions: clinical implications for targeted therapy.
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.
Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
Joshua R
JR
Bradish
Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
Justin D
JD
Richey
Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
Kristin M
KM
Post
Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
Kari
K
Meehan
Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
Joyashree D
JD
Sen
Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
Amanda J
AJ
Malek
1] Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA [2] Department of Pathology, Richard L Roudebush Veteran's Affairs Medical Center, Indianapolis, IN, USA.
Terrence M
TM
Katona
Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
Simon
S
Warren
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Theodore F
TF
Logan
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Leslie A
LA
Fecher
Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
Liang
L
Cheng
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf