BRAF, KIT, NRAS, GNAQ and GNA11 mutation analysis in cutaneous melanomas in Turkish population.
BACKGROUND
KIT and mitogen-activated protein kinase cascade are important for melanomagenesis. In the present study, we analyzed the frequency of BRAF, NRAS, KIT, GNAQ and GNA11 gene mutations and investigated their association with clinicopathological features of melanomas in Turkish population.


METHODS
Forty-seven primary cutaneous melanomas were included in our study. Sanger sequencing method was used for mutation analysis in all cases.


RESULTS
Mean age was 62.1 (29-101) years. Female:male ratio was 17:30. Among 47 melanomas, 14 (29.8%) BRAF, 10 (21.3%) NRAS, 4 (8.5%) KIT and 1(2.1%) GNAQ gene mutations were detected. Two of the KIT mutations were found in acral lentiginous melanoma (ALM). In the head and neck region, mutation frequency was significantly lower than in other locations (P = 0.035). The only GNAQ gene mutation (p.Q209L) was detected in a melanoma arising from blue nevus located on the scalp. None of the melanomas harbored NRAS exon 2, KIT exon 13/17/18, GNAQ exon 4 and GNA11 exon 4/5 mutations. Overall mutation frequency did not show significant difference between metastatic (8/14, 57.1%) and nonmetastatic (18/33, 54.5%) patients. We did not observe any significant association between mutation status and gender or age of various patients.


CONCLUSIONS
Our results support that BRAF and NRAS gene mutations are common in cutaneous melanomas. The activating mutations of KIT gene are rare and especially seen in ALM. GNAQ and GNA11 mutations are infrequent in cutaneous melanomas and may be associated only with melanomas arising from blue nevus.
Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey.
Ismail
I
Yilmaz
Mehmet
M
Gamsizkan
Zafer
Z
Kucukodaci
Ufuk
U
Berber
Dilaver
D
Demirel
Aptullah
A
Haholu
Gizem
G
Narli
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000235:genetics*; D014421:Turkey; D055815:Young Adult
D011518:Proto-Oncogene Proteins; D011494:Protein Kinases; D019204:GTP-Binding Proteins