title: Molecular alterations in malignant blue nevi and related blue lesions.
abstract: Malignant blue nevi (MBN) are extremely rare dermal melanocytic tumors that arise in association with atypical cellular blue nevi (ACBN), cellular blue nevi (CBN), common blue nevi (BN), or de novo. The frequency of BRAF, NRAS, and KIT mutations in malignant melanoma varies according to histological subtype and localization. These mutations are rarely observed in blue nevi, which have recently been shown to carry activating mutations in GNAQ/GNA11 genes. Only few small molecular studies of MBN have been published. The aim of the present study was to analyze in MBN and related blue lesions such as ACBN, CBN, and BN the prevalence of BRAF, NRAS, KIT, GNAQ, and GNA11 gene mutations and their association with clinicopathological features. We included in our study 12 MBN, 6 ACBN, 29 CBN, and 35 common BN diagnosed between 1996 and 2014. Sanger sequencing method was used for mutation analysis. Overall, GNAQ exon 5 mutation was the most frequent alteration (46 %), in 2 of 12 (17 %) MBN, 1 of 6 (17 %) ACBN, 22 of 29 (76 %) CBN, and 13 of 35 (37 %) common BN. BRAF V600E and GNA11 exon 5 mutations were respectively detected in 3 of 12 (25 %) and in 2 of 12 (17 %) MBN while none in ACBN, CBN, and common BN. None of the cases harbored NRAS exon 2/3, KIT exon 9/11/13/17/18, or GNAQ/GNA11 exon 4 mutations. GNAQ gene exon 5 mutations are rare in MBN and ACBN but frequent in CBN and common BN. Remarkably, BRAF V600E and GNA11 exon 5 mutations were only detected in MBN, whereas none were found in ACBN, CBN, or common BN. Our data contribute new elements to the limited data on molecular alterations in MBN.
authors.affiliation: Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey. isyilmaz@gata.edu.tr.
authors.forename: Ismail
authors.initials: I
authors.lastname: Yilmaz
authors.affiliation: Department of Pathology, Erzurum Military Hospital, Erzurum, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Gamsizkan
authors.affiliation: Istanbul Faculty of Medicine, Department of Pathology, Istanbul University, Istanbul, Turkey.
authors.forename: Sule Ozturk
authors.initials: SO
authors.lastname: Sari
authors.affiliation: Faculty of Medicine, Department of Pathology, Ege University, Izmir, Turkey.
authors.forename: Banu
authors.initials: B
authors.lastname: Yaman
authors.affiliation: Cerrahpasa Faculty of Medicine, Department of Pathology, Istanbul University, Istanbul, Turkey.
authors.forename: Cuyan
authors.initials: C
authors.lastname: Demirkesen
authors.affiliation: Faculty of Medicine, Department of Pathology, Ankara University, Ankara, Turkey.
authors.forename: Aylin
authors.initials: A
authors.lastname: Heper
authors.affiliation: Department of Pathology, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey.
authors.forename: Aylin Orgen
authors.initials: AO
authors.lastname: Calli
authors.affiliation: Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey.
authors.forename: Gizem
authors.initials: G
authors.lastname: Narli
authors.affiliation: Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey.
authors.forename: Zafer
authors.initials: Z
authors.lastname: Kucukodaci
authors.affiliation: Department of Pathology, Corlu Military Hospital, Corlu, Tekirdag, Turkey.
authors.forename: Ufuk
authors.initials: U
authors.lastname: Berber
authors.affiliation: Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey.
authors.forename: Dilaver
authors.initials: D
authors.lastname: Demirel
authors.affiliation: Faculty of Medicine, Department of Pathology, Ege University, Izmir, Turkey.
authors.forename: Taner
authors.initials: T
authors.lastname: Akalin
authors.affiliation: Faculty of Medicine, Department of Pathology, Gulhane Military Medical Academy, Ankara, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Demiriz
authors.affiliation: Istanbul Faculty of Medicine, Department of Pathology, Istanbul University, Istanbul, Turkey.
authors.forename: Nesimi
authors.initials: N
authors.lastname: Buyukbabani
keywords: BRAF; Blue nevi; GNA11; GNAQ; Malignant; Mutation