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Mutational profile of GNAQQ209 in human tumors
Simona Lamba1, Lara Felicioni, Fiamma Buttitta
1Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, University of Torino Medical School, University of Torino, Medical School Candiolo, Torino, Italy.
Background:
Frequent somatic mutations have recently been identified in the ras-like domain of the heterotrimeric G protein alpha-subunit (GNAQ) in blue naevi 83%, malignant blue naevi (50%) and ocular melanoma of the uvea (46%). The mutations exclusively affect codon 209 and result in GNAQ constitutive activation which, in turn, acts as a dominant oncogene.
Methodology:
To assess if the mutations are present in other tumor types we performed a systematic mutational profile of the GNAQ exon 5 in a panel of 922 neoplasms, including glioblastoma, gastrointestinal stromal tumors (GIST), acute myeloid leukemia (AML), blue naevi, skin melanoma, bladder, breast, colorectal, lung, ovarian, pancreas, and thyroid carcinomas.
Principal Findings:
We detected the previously reported mutations in 6/13 (46%) blue naevi. Changes affecting Q209 were not found in any of the other tumors. Our data indicate that the occurrence of GNAQ mutations display a unique pattern being present in a subset of melanocytic tumors but not in malignancies of glial, epithelial and stromal origin analyzed in this study.
Insights
Mutations in the GNAQ gene, specifically at codon 209, are frequently found in blue naevi and ocular melanoma. These GNAQ mutations were not detected in a broad range of other cancer types.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Somatic mutations in the GNAQ gene's ras-like domain are common in blue naevi (83%), malignant blue naevi (50%), and uveal melanoma (46%).
- These mutations specifically target codon 209, leading to constitutive activation of GNAQ, functioning as a dominant oncogene.
Purpose of the Study:
- To investigate the prevalence of GNAQ exon 5 mutations in a diverse panel of 922 neoplasms.
- To determine if GNAQ mutations are exclusive to melanocytic tumors or present in other malignancies.
Main Methods:
- Systematic mutational profiling of GNAQ exon 5 was conducted.
- A comprehensive panel of 922 tumors was analyzed, including various carcinomas, melanomas, glioblastoma, GIST, and AML.
Main Results:
- The previously identified GNAQ Q209 mutations were confirmed in 46% of blue naevi.
- No GNAQ Q209 mutations were detected in any of the other analyzed tumor types, including glial, epithelial, and stromal cancers.
Conclusions:
- GNAQ mutations exhibit a unique pattern, predominantly occurring in a subset of melanocytic tumors.
- The findings suggest GNAQ mutations are not a common driver in the investigated non-melanocytic malignancies.
