Abstract 101: Analysis of GNAQ mutations in subtypes of malignant melanoma

Abstract

Abstract Background: The MAP kinase pathway has been implicated in the pathogenesis of cutaneous melanoma, and mutations in BRAF and NRAS are commonly found in subtypes of melanomas as well as in benign nevi. Recently, several publications have reported frequent mutations in codon 209 of GNAQ in blue nevi and uveal melanoma, revealing an alternative path to MAP kinase activation. Aim of study: We wanted to investigate the prevalence of GNAQ mutations in codon 209 in a broad spectre of cutaneous melanoma, previously screened for mutations in BRAF, NRAS and EGFR. Methods: 75 benign and malignant tumors of different subgroups were collected at the Department of Pathology, the Gade Institute, Haukeland University Hospital, including: Spitz nevi, superficial spreading melanoma, superficial spreading melanoma in situ, lentigo malignant melanoma, nodular melanoma, metastases from nodular melanoma and uveal melanoma. Additionally, 14 acral African melanomas were collected at the Department of Pathology, Muhimbili University college of Health Sciences, Dar Es Salaam, Tanzania. Tumor tissue was manually dissected from formalin fixated paraffin-embedded sections, before GNAQ exon 5 was screened for mutations in codon 209 by direct Sanger sequencing. Further sample collection and analysis are ongoing. Results: The sequence analysis detected mutations in codon 209 in all five uveal melanomas tested (four harbored a Q209L mutation, and one had a Q209P mutation). However no mutations were found in any of the other subtypes of malignant melanoma. Conclusion: Our study shows that there appears to be a general lack of GNAQ mutations in cutaneous melanoma. This confirms that there may be different routes to MAP kinase activation in malignant melanoma as suggested by other studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 101. doi:1538-7445.AM2012-101