Oncogenic mutations in melanomas and benign melanocytic nevi of the female genital tract.
BACKGROUND
The genetic heterogeneity of melanomas and melanocytic nevi of the female genital tract is poorly understood.


OBJECTIVE
We aim to characterize the frequency of mutations of the following genes: BRAF, NRAS, KIT, GNA11, and GNAQ in female genital tract melanomas. We also characterize the frequency of BRAF mutations in female genital tract melanomas compared with melanocytic nevi.


METHODS
Mutational screening was performed on the following female genital tract melanocytic neoplasms: 25 melanomas, 7 benign melanocytic nevi, and 4 atypical melanocytic nevi.


RESULTS
Of the 25 female genital tract melanoma specimens queried, KIT mutations were detected in 4 (16.0%), NRAS mutations in 4 (16.0%), and BRAF mutations in 2 (8.0%) samples. Two of the tumors with KIT mutations harbored double mutations in the same exon. No GNAQ or GNA11 mutations were identified among 11 melanomas screened. BRAF V600E mutations were detected in 7 of 7 benign melanocytic genital nevi (100%) and 3 of 4 atypical genital nevi (75%).


CONCLUSIONS
Our study is limited by the small sample size of this rare subset of melanomas.


CONCLUSIONS
KIT, NRAS, and BRAF mutations are found in a subset of female genital tract melanomas. Screening for oncogenic mutations is important for developing and applying clinical therapies for melanomas of the female genital tract.
Harvard University, Cambridge, Massachusetts; Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Diane
D
Tseng
Department of Dermatology, Duke University Medical Center, Durham, North Carolina.
Julie
J
Kim
Knight Diagnostic Laboratories, Oregon Health and Science University, Portland, Oregon.
Andrea
A
Warrick
Knight Diagnostic Laboratories, Oregon Health and Science University, Portland, Oregon.
Dylan
D
Nelson
Knight Diagnostic Laboratories, Oregon Health and Science University, Portland, Oregon.
Marina
M
Pukay
Knight Diagnostic Laboratories, Oregon Health and Science University, Portland, Oregon.
Carol
C
Beadling
Division of Hematology and Oncology, Oregon Health and Science University, Portland, Oregon.
Michael
M
Heinrich
Department of Dermatology, Duke University Medical Center, Durham, North Carolina.
Maria Angelica
MA
Selim
Knight Diagnostic Laboratories, Oregon Health and Science University, Portland, Oregon.
Christopher L
CL
Corless
Department of Dermatology, Duke University Medical Center, Durham, North Carolina. Electronic address: kelly.nelson@dm.duke.edu.
Kelly
K
Nelson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D005833:Genital Neoplasms, Female / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009508:Nevus, Pigmented / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012189:Retrospective Studies
D004273:DNA, Neoplasm; C554062:GNA11 protein, human; C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
BRAF; KIT; NRAS; female genital melanomas; female genital nevi; oncogenic mutations