GNAQ Gene Status in Cellular Blue Nevi, Spitzoid and Spindle Cell Melanomas.
Sirish Vullaganti, Patricia DeVilliers, Tatyana Isayeva, Aleodor Andea. University of Alabama at Birmingham
Background: Most benign and malignant melanocytic neoplasms display constitutive activation of the mitogen-activated protein (MAP) kinase pathway through mutations in BRAF, NRAS or HRAS genes. Recently, frequent somatic mutations of codon 209 (Q209L) in the heterotrimeric G protein a-subunit (GNAQ) gene have been reported in blue nevi (BNs) and uveal melanomas as an alternative route to MAP kinase activation. Since BNs are a heterogeneous group including common, cellular and atypical variants we aimed to investigate the differential presence of GNAQ activating mutations in BN variants which has not been reported before. In addition, GNAQ status was investigated in desmoplastic melanomas which are often confused with BNs and in Spitzoid melanomas which usually lack BRAF mutations.
Design: The study series included 9 BNs (common variant -2, cellular variant -5, atypical -1), 4 desmoplastic melanomas and 4 Spitzoid melanomas. Following microdissection of tumor from the formalin-fixed paraffin-embedded material and DNA extraction, direct sequencing of exon 5 of GNAQ gene was performed and codon 209 was analyzed for presence of the mutation.
Results: The results of mutational analysis are summarized in the table below.
|Common BN||Cellular BN||Atypical BN||Spindle Cell/Desmoplastic Melanoma||Spitzoid Melanoma|
|No. of cases||2||5||1||4||4|
|GNAQ mutation (%)||100%||0%||100%||0%||0%|